CA2953655C - Benzoxazinone amides as mineralocorticoid receptor modulators - Google Patents
Benzoxazinone amides as mineralocorticoid receptor modulators Download PDFInfo
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- CA2953655C CA2953655C CA2953655A CA2953655A CA2953655C CA 2953655 C CA2953655 C CA 2953655C CA 2953655 A CA2953655 A CA 2953655A CA 2953655 A CA2953655 A CA 2953655A CA 2953655 C CA2953655 C CA 2953655C
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- Prior art keywords
- dihydro
- benzoxazin
- mmol
- oxo
- compound
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- -1 Benzoxazinone amides Chemical class 0.000 title abstract description 70
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 title description 4
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 237
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 238000011282 treatment Methods 0.000 claims description 30
- 206010019280 Heart failures Diseases 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 208000020832 chronic kidney disease Diseases 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- WSOYYBRZDOKCSB-GFCCVEGCSA-N 2-[(3R)-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound FC1=CC2=C(N([C@@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 WSOYYBRZDOKCSB-GFCCVEGCSA-N 0.000 claims description 2
- MBKYLPOPYYLTNW-ZDUSSCGKSA-N 2-[(3S)-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound FC1=CC2=C(N([C@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 MBKYLPOPYYLTNW-ZDUSSCGKSA-N 0.000 claims 2
- POJKNBHEJAUGMR-CYBMUJFWSA-N 2-[(3R)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound BrC1=CC2=C(N([C@@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 POJKNBHEJAUGMR-CYBMUJFWSA-N 0.000 claims 1
- ONFNEWGKOKVUHI-GFCCVEGCSA-N 2-[(3R)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound BrC1=CC2=C(N([C@@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 ONFNEWGKOKVUHI-GFCCVEGCSA-N 0.000 claims 1
- PLOQCPGEMKIJBX-CYBMUJFWSA-N 2-[(3R)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound ClC1=CC2=C(N([C@@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 PLOQCPGEMKIJBX-CYBMUJFWSA-N 0.000 claims 1
- NWSIDHCBAFDSKX-GFCCVEGCSA-N 2-[(3R)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound ClC1=CC2=C(N([C@@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 NWSIDHCBAFDSKX-GFCCVEGCSA-N 0.000 claims 1
- MBKYLPOPYYLTNW-CYBMUJFWSA-N 2-[(3R)-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound FC1=CC2=C(N([C@@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 MBKYLPOPYYLTNW-CYBMUJFWSA-N 0.000 claims 1
- POJKNBHEJAUGMR-ZDUSSCGKSA-N 2-[(3S)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound BrC1=CC2=C(N([C@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 POJKNBHEJAUGMR-ZDUSSCGKSA-N 0.000 claims 1
- ONFNEWGKOKVUHI-LBPRGKRZSA-N 2-[(3S)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound BrC1=CC2=C(N([C@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 ONFNEWGKOKVUHI-LBPRGKRZSA-N 0.000 claims 1
- PLOQCPGEMKIJBX-ZDUSSCGKSA-N 2-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound ClC1=CC2=C(N([C@H](CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 PLOQCPGEMKIJBX-ZDUSSCGKSA-N 0.000 claims 1
- NWSIDHCBAFDSKX-LBPRGKRZSA-N 2-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound ClC1=CC2=C(N([C@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 NWSIDHCBAFDSKX-LBPRGKRZSA-N 0.000 claims 1
- WSOYYBRZDOKCSB-LBPRGKRZSA-N 2-[(3S)-7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound FC1=CC2=C(N([C@H](CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 WSOYYBRZDOKCSB-LBPRGKRZSA-N 0.000 claims 1
- ZHOMQPMDDHOJBC-UHFFFAOYSA-N 2-[4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound O=C1COC2=C(N1)C=C(C=C2)C(=O)N1C(COC2=C1C=CC=C2)CC(=O)N ZHOMQPMDDHOJBC-UHFFFAOYSA-N 0.000 claims 1
- POJKNBHEJAUGMR-UHFFFAOYSA-N 2-[7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound BrC1=CC2=C(N(C(CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 POJKNBHEJAUGMR-UHFFFAOYSA-N 0.000 claims 1
- ONFNEWGKOKVUHI-UHFFFAOYSA-N 2-[7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound BrC1=CC2=C(N(C(CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 ONFNEWGKOKVUHI-UHFFFAOYSA-N 0.000 claims 1
- PLOQCPGEMKIJBX-UHFFFAOYSA-N 2-[7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound ClC1=CC2=C(N(C(CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 PLOQCPGEMKIJBX-UHFFFAOYSA-N 0.000 claims 1
- NWSIDHCBAFDSKX-UHFFFAOYSA-N 2-[7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound ClC1=CC2=C(N(C(CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 NWSIDHCBAFDSKX-UHFFFAOYSA-N 0.000 claims 1
- MBKYLPOPYYLTNW-UHFFFAOYSA-N 2-[7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide Chemical compound FC1=CC2=C(N(C(CO2)CC(=O)NC)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 MBKYLPOPYYLTNW-UHFFFAOYSA-N 0.000 claims 1
- WSOYYBRZDOKCSB-UHFFFAOYSA-N 2-[7-fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound FC1=CC2=C(N(C(CO2)CC(=O)N)C(=O)C=2C=CC3=C(NC(CO3)=O)C=2)C=C1 WSOYYBRZDOKCSB-UHFFFAOYSA-N 0.000 claims 1
- GNKWYKHEEWCEKY-CYBMUJFWSA-N N-methyl-2-[(3R)-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound CNC(C[C@@H]1COC2=C(N1C(=O)C=1C=CC3=C(NC(CO3)=O)C=1)C=CC=C2)=O GNKWYKHEEWCEKY-CYBMUJFWSA-N 0.000 claims 1
- GNKWYKHEEWCEKY-ZDUSSCGKSA-N N-methyl-2-[(3S)-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound CNC(C[C@H]1COC2=C(N1C(=O)C=1C=CC3=C(NC(CO3)=O)C=1)C=CC=C2)=O GNKWYKHEEWCEKY-ZDUSSCGKSA-N 0.000 claims 1
- GNKWYKHEEWCEKY-UHFFFAOYSA-N N-methyl-2-[4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetamide Chemical compound CNC(CC1COC2=C(N1C(=O)C=1C=CC3=C(NC(CO3)=O)C=1)C=CC=C2)=O GNKWYKHEEWCEKY-UHFFFAOYSA-N 0.000 claims 1
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- 239000002395 mineralocorticoid Substances 0.000 abstract description 54
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Classifications
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- 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
- C07D413/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
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- 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
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
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- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- 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
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US201462018790P | 2014-06-30 | 2014-06-30 | |
| US62/018,790 | 2014-06-30 | ||
| PCT/GB2015/051860 WO2016001631A1 (en) | 2014-06-30 | 2015-06-26 | Benzoxazinone amides as mineralocorticoid receptor modulators |
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| CA2953655A1 CA2953655A1 (en) | 2016-01-07 |
| CA2953655C true CA2953655C (en) | 2020-05-12 |
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| CA2953655C (en) * | 2014-06-30 | 2020-05-12 | Astrazeneca Ab | Benzoxazinone amides as mineralocorticoid receptor modulators |
| SG11202100417RA (en) | 2018-07-19 | 2021-02-25 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
| CN112107568B (zh) * | 2019-06-19 | 2022-03-25 | 北京龙嘉博创医药科技有限公司 | 二芳基酰胺类化合物及其应用 |
| MX2020005388A (es) | 2019-08-30 | 2022-10-25 | Astrazeneca Ab | Uso de composiciones farmacéuticas que comprenden dapagliflozina e inhibidores de sglt2. |
| TW202220672A (zh) | 2020-07-27 | 2022-06-01 | 瑞典商阿斯特捷利康公司 | 用達格列淨治療慢性腎臟病之方法 |
| TWI808786B (zh) * | 2021-06-15 | 2023-07-11 | 大陸商正大天晴藥業集團股份有限公司 | 酮類衍生物 |
| TW202409023A (zh) | 2022-07-14 | 2024-03-01 | 美商富曼西公司 | 除草苯并𠯤 |
| CR20250276A (es) | 2022-09-01 | 2025-09-04 | Astrazeneca Ab | Combinación de inhibidores de sglt2 y moduladores del receptor mineralcorticoide para usar en el tratamiento de enfermedades cardiorrenales (divisional 2025-0112) |
| WO2024125591A1 (zh) * | 2022-12-15 | 2024-06-20 | 正大天晴药业集团股份有限公司 | 苯并恶嗪酮类化合物的结晶及其制备 |
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| WO2002085868A1 (en) * | 2001-04-23 | 2002-10-31 | Astrazeneca Ab | Benzoxazinone derivatives for use in the treatment of angiogenesis |
| WO2004056820A1 (en) * | 2002-12-20 | 2004-07-08 | Warner-Lambert Company Llc | Benzoxazines and derivatives thereof as inhibitors of pi3ks |
| JP2008506689A (ja) * | 2004-07-14 | 2008-03-06 | リガンド・ファーマシューティカルズ・インコーポレイテッド | 細胞間受容体のモジュレーター化合物および方法 |
| RU2007107177A (ru) * | 2004-07-28 | 2008-09-10 | Айрм Ллк (Bm) | Соединения и композиции, как модуляторы ядерных рецепторов стероидных гормонов |
| AR056893A1 (es) | 2005-12-28 | 2007-10-31 | Takeda Pharmaceutical | Compuestos heterociclicos fusionados y no fusionados, antagonistas de receptores mineralocorticoides |
| TWI385161B (zh) | 2006-02-02 | 2013-02-11 | Mitsubishi Tanabe Pharma Corp | 含氮雜雙環化合物 |
| WO2008053300A1 (en) | 2006-10-31 | 2008-05-08 | Pfizer Products Inc. | Pyrazoline compounds as mineralocorticoid receptor antagonists |
| DE102007009494A1 (de) | 2007-02-27 | 2008-08-28 | Bayer Healthcare Ag | Substituierte 4-Aryl-1, 4-dihydro-1,6-naphthyridinamide und ihre Verwendung |
| JP2010522168A (ja) | 2007-03-23 | 2010-07-01 | メルク・シャープ・エンド・ドーム・コーポレイション | 鉱質コルチコイドレセプターモジュレータ |
| BRPI0809656B8 (pt) | 2007-04-09 | 2021-05-25 | Daiichi Sankyo Co Ltd | atropisômero, composto, agente profilático ou terapêutico, e, composição farmacêutica |
| JP5173653B2 (ja) * | 2007-08-01 | 2013-04-03 | 田辺三菱製薬株式会社 | 医薬組成物 |
| US8258131B2 (en) | 2007-08-01 | 2012-09-04 | Mitsubishi Tanabe Pharma Corporation | Fused bicyclic compound |
| PE20091057A1 (es) | 2007-12-19 | 2009-07-20 | Lilly Co Eli | Antagonistas del receptor mineralcorticoide y metodos de uso |
| WO2009154557A1 (en) * | 2008-06-18 | 2009-12-23 | Astrazeneca Ab | Benzoxazinone derivatives acting as beta2-adrenoreceptor agonist for the treatment of respiratory disorders |
| US20100094000A1 (en) | 2008-09-03 | 2010-04-15 | Takeda Pharmaceutical Company Limited | Pyrazole compounds |
| WO2010098286A1 (ja) | 2009-02-25 | 2010-09-02 | 第一三共株式会社 | ミネラルコルチコイド受容体拮抗薬を含有する医薬 |
| KR101312179B1 (ko) | 2009-03-12 | 2013-09-26 | 일라이 릴리 앤드 캄파니 | 미네랄로코르티코이드 수용체 길항제 및 사용 방법 |
| WO2010116282A1 (en) | 2009-04-10 | 2010-10-14 | Pfizer Inc. | 4, 5-dihydro-lh-pyrazole compounds and their pharmaceutical uses |
| EP2569576B1 (en) | 2010-05-11 | 2016-07-06 | Koninklijke Philips N.V. | Lighting module |
| CA2798831A1 (en) | 2010-05-11 | 2011-11-17 | Pfizer Inc. | Morpholine compounds as mineralocorticoid receptor antagonists |
| JPWO2012008435A1 (ja) | 2010-07-13 | 2013-09-09 | 大日本住友製薬株式会社 | ビアリールアミド誘導体またはその薬理学的に許容される塩 |
| EP2638012A1 (en) | 2010-11-10 | 2013-09-18 | Boehringer Ingelheim International GmbH | Pyridyl ureas as mineralocorticoid receptor antagonists |
| CA2953655C (en) * | 2014-06-30 | 2020-05-12 | Astrazeneca Ab | Benzoxazinone amides as mineralocorticoid receptor modulators |
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