CA2729050A1 - Diaryl ureas for treating heart failure - Google Patents
Diaryl ureas for treating heart failure Download PDFInfo
- Publication number
- CA2729050A1 CA2729050A1 CA2729050A CA2729050A CA2729050A1 CA 2729050 A1 CA2729050 A1 CA 2729050A1 CA 2729050 A CA2729050 A CA 2729050A CA 2729050 A CA2729050 A CA 2729050A CA 2729050 A1 CA2729050 A1 CA 2729050A1
- Authority
- CA
- Canada
- Prior art keywords
- inhibitors
- formula
- optionally substituted
- alkyl
- insufficiency
- 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.)
- Abandoned
Links
- -1 Diaryl ureas Chemical class 0.000 title claims abstract description 77
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 42
- 235000013877 carbamide Nutrition 0.000 title description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 29
- 201000010099 disease Diseases 0.000 claims abstract description 25
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 128
- 239000003112 inhibitor Substances 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims description 20
- 238000003786 synthesis reaction Methods 0.000 claims description 20
- 239000005557 antagonist Substances 0.000 claims description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 14
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 14
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000013543 active substance Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 11
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 229940074391 gallic acid Drugs 0.000 claims description 10
- 235000004515 gallic acid Nutrition 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
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- 125000001624 naphthyl group Chemical group 0.000 claims description 10
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- 208000009525 Myocarditis Diseases 0.000 claims description 9
- 206010030113 Oedema Diseases 0.000 claims description 9
- 230000007547 defect Effects 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 210000003709 heart valve Anatomy 0.000 claims description 9
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 8
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 8
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Chemical group 0.000 claims description 8
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- 239000011737 fluorine Substances 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 210000002216 heart Anatomy 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 239000002207 metabolite Substances 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 7
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 7
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 7
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 150000003536 tetrazoles Chemical class 0.000 claims description 7
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 7
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 6
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- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 claims description 6
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- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 claims description 5
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Classifications
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- 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
- A61K31/435—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/10—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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08011471.3 | 2008-06-25 | ||
| EP08011471 | 2008-06-25 | ||
| PCT/EP2009/004390 WO2009156089A1 (en) | 2008-06-25 | 2009-06-18 | Diaryl ureas for treating heart failure |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2729050A1 true CA2729050A1 (en) | 2009-12-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2729050A Abandoned CA2729050A1 (en) | 2008-06-25 | 2009-06-18 | Diaryl ureas for treating heart failure |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20110263657A1 (enExample) |
| EP (1) | EP2293792A1 (enExample) |
| JP (1) | JP2011525506A (enExample) |
| KR (1) | KR20110031294A (enExample) |
| CN (1) | CN102076338A (enExample) |
| AU (1) | AU2009262599A1 (enExample) |
| BR (1) | BRPI0914636A2 (enExample) |
| CA (1) | CA2729050A1 (enExample) |
| IL (1) | IL209647A0 (enExample) |
| MX (1) | MX2010014441A (enExample) |
| RU (1) | RU2011102471A (enExample) |
| WO (1) | WO2009156089A1 (enExample) |
| ZA (1) | ZA201009063B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102718703B (zh) * | 2011-03-31 | 2016-09-14 | 中国医学科学院药物研究所 | Gk和ppar双重激动活性的含有二甲基的芳基脲类衍生物 |
| JP2014527511A (ja) | 2011-06-24 | 2014-10-16 | アムジエン・インコーポレーテツド | Ｔｒｐｍ８拮抗剤及び治療におけるそれらの使用 |
| EP2723718A1 (en) | 2011-06-24 | 2014-04-30 | Amgen Inc. | Trpm8 antagonists and their use in treatments |
| US8952009B2 (en) | 2012-08-06 | 2015-02-10 | Amgen Inc. | Chroman derivatives as TRPM8 inhibitors |
| RU2646454C2 (ru) * | 2013-11-12 | 2018-03-05 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" | Способ моделирования алкогольной кардиомиопатии |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE602004011340T2 (de) * | 2003-05-20 | 2008-11-06 | Bayer Healthcare Llc | Diaryl-harnstoffe mit kinasehemmender wirkung |
| NZ544920A (en) * | 2003-07-23 | 2009-11-27 | Bayer Healthcare Llc | 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide and metabolites for the treatment and prevention of diseases and conditions |
| US20090197922A1 (en) * | 2006-01-24 | 2009-08-06 | The University Of Chicago | Compositions and methods for treating pulmonary hypertension |
| WO2009092442A1 (en) * | 2008-01-23 | 2009-07-30 | Universidad De Barcelona | Treatment of portal hypertension and related conditions by combined inhibition of the vegf and pdgf signalling pathways |
-
2009
- 2009-06-18 US US13/001,145 patent/US20110263657A1/en not_active Abandoned
- 2009-06-18 CN CN2009801240616A patent/CN102076338A/zh active Pending
- 2009-06-18 WO PCT/EP2009/004390 patent/WO2009156089A1/en not_active Ceased
- 2009-06-18 AU AU2009262599A patent/AU2009262599A1/en not_active Abandoned
- 2009-06-18 CA CA2729050A patent/CA2729050A1/en not_active Abandoned
- 2009-06-18 BR BRPI0914636A patent/BRPI0914636A2/pt not_active IP Right Cessation
- 2009-06-18 JP JP2011515168A patent/JP2011525506A/ja not_active Withdrawn
- 2009-06-18 RU RU2011102471/15A patent/RU2011102471A/ru not_active Application Discontinuation
- 2009-06-18 MX MX2010014441A patent/MX2010014441A/es not_active Application Discontinuation
- 2009-06-18 EP EP09768938A patent/EP2293792A1/en not_active Withdrawn
- 2009-06-18 KR KR1020107029143A patent/KR20110031294A/ko not_active Withdrawn
-
2010
- 2010-11-30 IL IL209647A patent/IL209647A0/en unknown
- 2010-12-17 ZA ZA2010/09063A patent/ZA201009063B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0914636A2 (pt) | 2015-10-20 |
| JP2011525506A (ja) | 2011-09-22 |
| IL209647A0 (en) | 2011-02-28 |
| MX2010014441A (es) | 2011-01-21 |
| ZA201009063B (en) | 2012-02-29 |
| KR20110031294A (ko) | 2011-03-25 |
| CN102076338A (zh) | 2011-05-25 |
| RU2011102471A (ru) | 2012-07-27 |
| EP2293792A1 (en) | 2011-03-16 |
| US20110263657A1 (en) | 2011-10-27 |
| WO2009156089A1 (en) | 2009-12-30 |
| AU2009262599A1 (en) | 2009-12-30 |
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| FZDE | Discontinued |
Effective date: 20140618 |