CA2710409C - 6h-dibenz0 [b,e] oxepine derived nonsteroidal mineralocorticoid receptor antagonists - Google Patents
6h-dibenz0 [b,e] oxepine derived nonsteroidal mineralocorticoid receptor antagonists Download PDFInfo
- Publication number
- CA2710409C CA2710409C CA2710409A CA2710409A CA2710409C CA 2710409 C CA2710409 C CA 2710409C CA 2710409 A CA2710409 A CA 2710409A CA 2710409 A CA2710409 A CA 2710409A CA 2710409 C CA2710409 C CA 2710409C
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- CA
- Canada
- Prior art keywords
- compound
- ylidene
- formula
- methyl
- oxepin
- 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.)
- Expired - Fee Related
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- 239000002394 mineralocorticoid antagonist Substances 0.000 title description 3
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- 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims description 53
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- 239000001257 hydrogen Substances 0.000 claims description 28
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
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- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 10
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- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- MMPWHAJQEZIIEH-YUMQZZPRSA-N tert-butyl (1s,6s)-7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]2O[C@H]21 MMPWHAJQEZIIEH-YUMQZZPRSA-N 0.000 description 1
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- TYVPMGGBXKDZAF-HTQZYQBOSA-N tert-butyl (2r,4r)-4-azido-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](N=[N+]=[N-])C[C@@H]1CO TYVPMGGBXKDZAF-HTQZYQBOSA-N 0.000 description 1
- OCLZOKUGIXLYJZ-JGVFFNPUSA-N tert-butyl (2r,4s)-4-amino-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](N)C[C@@H]1CO OCLZOKUGIXLYJZ-JGVFFNPUSA-N 0.000 description 1
- OGLXDTLKKWBMPK-RYUDHWBXSA-N tert-butyl (2s,4s)-4-(4-bromo-2-nitroanilino)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound C1[C@@H](CO)N(C(=O)OC(C)(C)C)C[C@H]1NC1=CC=C(Br)C=C1[N+]([O-])=O OGLXDTLKKWBMPK-RYUDHWBXSA-N 0.000 description 1
- OCLZOKUGIXLYJZ-YUMQZZPRSA-N tert-butyl (2s,4s)-4-amino-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](N)C[C@H]1CO OCLZOKUGIXLYJZ-YUMQZZPRSA-N 0.000 description 1
- ITPHGVPTTDIMDB-CVEARBPZSA-N tert-butyl (3r,4r)-3-hydroxy-4-(2-phenylethyl)piperidine-1-carboxylate Chemical compound O[C@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1CCC1=CC=CC=C1 ITPHGVPTTDIMDB-CVEARBPZSA-N 0.000 description 1
- DCYVVDAIMLJKKF-DHLKQENFSA-N tert-butyl (3r,4r)-4-benzyl-3-hydroxy-4-(2-phenylethyl)piperidine-1-carboxylate Chemical compound O[C@H]1CN(C(=O)OC(C)(C)C)CC[C@]1(CC=1C=CC=CC=1)CCC1=CC=CC=C1 DCYVVDAIMLJKKF-DHLKQENFSA-N 0.000 description 1
- LWHRDKRVPKNHQP-YPMHNXCESA-N tert-butyl (3r,4s)-3-(4-bromo-2-nitroanilino)-4-hydroxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@H](O)[C@@H]1NC1=CC=C(Br)C=C1[N+]([O-])=O LWHRDKRVPKNHQP-YPMHNXCESA-N 0.000 description 1
- LWHRDKRVPKNHQP-WCQYABFASA-N tert-butyl (3s,4r)-3-(4-bromo-2-nitroanilino)-4-hydroxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@@H](O)[C@H]1NC1=CC=C(Br)C=C1[N+]([O-])=O LWHRDKRVPKNHQP-WCQYABFASA-N 0.000 description 1
- MOZOQDNRVPHFOO-BQBZGAKWSA-N tert-butyl (3s,4s)-3-amino-4-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@H](N)[C@@H](O)C1 MOZOQDNRVPHFOO-BQBZGAKWSA-N 0.000 description 1
- ITPHGVPTTDIMDB-JKSUJKDBSA-N tert-butyl (3s,4s)-3-hydroxy-4-(2-phenylethyl)piperidine-1-carboxylate Chemical compound O[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1CCC1=CC=CC=C1 ITPHGVPTTDIMDB-JKSUJKDBSA-N 0.000 description 1
- DNVDJTZLMZISEU-VKGZEUJTSA-N tert-butyl (3s,4s)-3-hydroxy-4-(2-phenylethyl)piperidine-1-carboxylate;(2r,3r)-2,3-dihydroxybutanedioic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.O[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1CCC1=CC=CC=C1 DNVDJTZLMZISEU-VKGZEUJTSA-N 0.000 description 1
- OLMYDBBHYVEIME-DHLKQENFSA-N tert-butyl (3s,4s)-4-(benzylamino)-3-hydroxy-4-(2-phenylethyl)piperidine-1-carboxylate Chemical compound O[C@H]1CN(C(=O)OC(C)(C)C)CC[C@@]1(NCC=1C=CC=CC=1)CCC1=CC=CC=C1 OLMYDBBHYVEIME-DHLKQENFSA-N 0.000 description 1
- KREUZCYJWPQPJX-YUMQZZPRSA-N tert-butyl (3s,4s)-4-amino-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)[C@@H](O)C1 KREUZCYJWPQPJX-YUMQZZPRSA-N 0.000 description 1
- WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- YWWDBCBWQNCYNR-UHFFFAOYSA-N trimethylphosphine Chemical compound CP(C)C YWWDBCBWQNCYNR-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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- 239000003039 volatile agent Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- 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
- A61P5/00—Drugs for disorders of the endocrine system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/40—Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1477607P | 2007-12-19 | 2007-12-19 | |
| US61/014,776 | 2007-12-19 | ||
| PCT/US2008/085997 WO2009085584A1 (en) | 2007-12-19 | 2008-12-09 | 6h-dibenz0 [b, e] oxepine derived nonsteroidal mineralocorticoid receptor antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2710409A1 CA2710409A1 (en) | 2009-07-09 |
| CA2710409C true CA2710409C (en) | 2012-11-06 |
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| CA2710409A Expired - Fee Related CA2710409C (en) | 2007-12-19 | 2008-12-09 | 6h-dibenz0 [b,e] oxepine derived nonsteroidal mineralocorticoid receptor antagonists |
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| WO2009018657A1 (en) | 2007-08-03 | 2009-02-12 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
| EP2234977A4 (en) | 2007-12-19 | 2011-04-13 | Boehringer Ingelheim Int | VIRAL POLYMERASE INHIBITORS |
| WO2010104721A1 (en) * | 2009-03-12 | 2010-09-16 | Eli Lilly And Company | Mineralocorticoid receptor antagonist and methods of use |
| EP2568986B1 (en) | 2010-05-10 | 2016-01-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for the treatment of fluid accumulation in and/ or under the retina |
| EP2582365B1 (en) | 2010-06-16 | 2019-03-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions for stimulating reepithelialisation during wound healing |
| CN102060670A (zh) * | 2011-01-04 | 2011-05-18 | 常州大学 | 一种2-溴-6-氟苯甲醇的制备方法 |
| MD20150103A2 (ro) | 2013-05-02 | 2016-02-29 | Pfizer Inc. | Derivaţi ai imidazo-triazinei ca inhibitori ai PDE10 |
| AR099416A1 (es) | 2014-02-28 | 2016-07-20 | Lilly Co Eli | Terapia combinada para la hipertensión resistente |
| ME03316B (me) | 2014-06-30 | 2019-10-20 | Astrazeneca Ab | Benzoksazinon amidi као modulatori mineralokorтikoidnog receptora |
| JP2017531684A (ja) * | 2014-11-21 | 2017-10-26 | イーライ リリー アンド カンパニー | 腎障害の治療のための１，２−ベンゾチアゾール化合物 |
| US20180280414A1 (en) | 2015-10-13 | 2018-10-04 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for the treatment of choroidal neovascularisation |
| EP3490606B8 (en) | 2016-07-26 | 2024-04-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antagonist of mineralocorticoid receptor for the treatment of osteoarthritis |
| WO2018054357A1 (zh) * | 2016-09-24 | 2018-03-29 | 山东亨利医药科技有限责任公司 | 含盐皮质激素受体拮抗剂的药物组合物及其用途 |
| EP4118235B1 (en) | 2020-03-11 | 2026-08-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of determining whether a subject has or is at risk of having a central serous chorioretinopathy |
| WO2023031277A1 (en) | 2021-08-31 | 2023-03-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of ocular rosacea |
| CN117510398A (zh) * | 2023-11-02 | 2024-02-06 | 上海诺丁太生物科技有限公司 | 一种高光学纯度(3r,4r)/(3s,4s)-n-boc-4-氨基-3-羟基哌啶的制备方法 |
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| US4072756A (en) * | 1973-05-17 | 1978-02-07 | Sandoz Ltd. | Tricyclo piperidino ketones and soporific compositions thereof |
| SE426341C (sv) * | 1980-02-14 | 1985-09-23 | Fagersta Ab | Sett att forhindra korrosion i en forbrenningsanleggnings kylare och skorsten vid kylning av rokgaser |
| FR2603713B1 (fr) * | 1986-09-10 | 1992-07-24 | Canon Kk | Derive nouveau de 5h-dibenzo(a,d)cycloheptane-(ene)ylidene, son procede de production et support electrophotographique photosensible le contenant |
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| GB8914061D0 (en) * | 1989-06-19 | 1989-08-09 | Wellcome Found | Agents for potentiating the effects of antitumour agents and combating multiple drug resistance |
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| EP1154997A4 (en) | 1999-01-26 | 2002-11-04 | Dana Farber Cancer Inst Inc | PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF USE |
| ES2260497T7 (es) * | 2001-11-21 | 2009-11-05 | Millennium Pharmaceuticals, Inc. | Antagonistas de receptores de quimioquininas y metodos de uso de los mismos. |
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| WO2005066153A1 (en) | 2003-12-19 | 2005-07-21 | Eli Lilly And Company | Tricyclic steroid hormone nuclear receptor modulators |
| DE602004014640D1 (de) * | 2003-12-19 | 2008-08-07 | Lilly Co Eli | Tricyclische modulatoren von nuklearen steroidhormonrezeptoren |
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| RU2007107177A (ru) * | 2004-07-28 | 2008-09-10 | Айрм Ллк (Bm) | Соединения и композиции, как модуляторы ядерных рецепторов стероидных гормонов |
| SG161261A1 (en) | 2004-11-10 | 2010-05-27 | Incyte Corp | Lactam compounds and their use as pharmaceuticals |
| ES2375877T3 (es) | 2006-10-31 | 2012-03-07 | Pfizer Products Inc. | Compuestos de pirazolina como antagonistas de receptores de mineralocorticoides. |
| JP2010522732A (ja) | 2007-03-29 | 2010-07-08 | ナームローゼ・フエンノートチヤツプ・オルガノン | 鉱質コルチコイド受容体アンタゴニスト |
| PE20091339A1 (es) | 2007-12-21 | 2009-09-26 | Glaxo Group Ltd | Derivados de oxadiazol con actividad sobre receptores s1p1 |
| GB0725102D0 (en) | 2007-12-21 | 2008-01-30 | Glaxo Group Ltd | Compounds |
| WO2009094157A1 (en) | 2008-01-25 | 2009-07-30 | Arena Pharmaceuticals, Inc. | Dihydro- 1h- pyrrolo [1,2-a] indol-1-yl carboxylic derivatives which act as s1p1 agonists |
| WO2010104721A1 (en) | 2009-03-12 | 2010-09-16 | Eli Lilly And Company | Mineralocorticoid receptor antagonist and methods of use |
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