ES2548050T3 - Profármacos de derivados de imidazol moduladores de LXR - Google Patents
Profármacos de derivados de imidazol moduladores de LXR Download PDFInfo
- Publication number
- ES2548050T3 ES2548050T3 ES12711739.8T ES12711739T ES2548050T3 ES 2548050 T3 ES2548050 T3 ES 2548050T3 ES 12711739 T ES12711739 T ES 12711739T ES 2548050 T3 ES2548050 T3 ES 2548050T3
- Authority
- ES
- Spain
- Prior art keywords
- solvent
- compound
- lxr
- prodrugs
- forms
- 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.)
- Active
Links
- 150000002460 imidazoles Chemical class 0.000 title 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title 1
- 229940002612 prodrug Drugs 0.000 title 1
- 239000000651 prodrug Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract description 25
- 150000003839 salts Chemical class 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 description 16
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- -1 (4 '- (2- (1- (2,6-dichlorophenyl) -1-methylethyl) -4- (1-hydroxy-1 -methylethyl) -1H-imidazol-1-yl) -3,3'-difluoro-5 (methylsulfonyl) biphenyl-4-yl) methyl Chemical group 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
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- 210000002700 urine Anatomy 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 4
- 229960001596 famotidine Drugs 0.000 description 4
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- 229960000444 pentagastrin Drugs 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101001051093 Homo sapiens Low-density lipoprotein receptor Proteins 0.000 description 2
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- 238000002441 X-ray diffraction Methods 0.000 description 2
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- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
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- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
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- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 238000004482 13C cross polarization magic angle spinning Methods 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 101150092476 ABCA1 gene Proteins 0.000 description 1
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 1
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
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- 206010070901 Diabetic dyslipidaemia Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
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- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
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- 208000035475 disorder Diseases 0.000 description 1
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- 230000000694 effects Effects 0.000 description 1
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- 238000003379 elimination reaction Methods 0.000 description 1
- ZWMHKXYQHNWDRX-UHFFFAOYSA-N ethanol;propane-1,1-diol Chemical compound CCO.CCC(O)O ZWMHKXYQHNWDRX-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
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- 239000000706 filtrate Substances 0.000 description 1
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- 239000011521 glass Substances 0.000 description 1
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- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
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- 230000004060 metabolic process Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
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- 230000004141 reverse cholesterol transport Effects 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001622 two pulse phase modulation pulse sequence Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161467404P | 2011-03-25 | 2011-03-25 | |
| US201161467404P | 2011-03-25 | ||
| PCT/US2012/030499 WO2012135082A1 (en) | 2011-03-25 | 2012-03-26 | Prodrugs of lxr modulating imidazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2548050T3 true ES2548050T3 (es) | 2015-10-13 |
Family
ID=45926934
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12711739.8T Active ES2548050T3 (es) | 2011-03-25 | 2012-03-26 | Profármacos de derivados de imidazol moduladores de LXR |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8901106B2 (enExample) |
| EP (1) | EP2688871B1 (enExample) |
| JP (1) | JP2014510110A (enExample) |
| CN (1) | CN103443082B (enExample) |
| AR (1) | AR088728A1 (enExample) |
| ES (1) | ES2548050T3 (enExample) |
| TW (1) | TW201242953A (enExample) |
| WO (1) | WO2012135082A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| HUE046292T2 (hu) | 2012-08-13 | 2020-02-28 | Univ Rockefeller | Melanóma kezelése és diagnosztizálása |
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| ES2804304T3 (es) | 2013-09-04 | 2021-02-05 | Ellora Therapeutics Inc | Moduladores del receptor X hepático (LXR) |
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| JP7025022B2 (ja) | 2016-01-11 | 2022-02-24 | ザ ロックフェラー ユニバーシティー | 骨髄系由来抑制細胞関連障害の治療のための方法 |
| EA201892149A1 (ru) | 2016-04-01 | 2019-04-30 | Юсб Байофарма Спрл | Конденсированные пентациклические производные имидазола в качестве модуляторов активности tnf |
| WO2017167995A1 (en) | 2016-04-01 | 2017-10-05 | Ucb Biopharma Sprl | Fused hexacyclic imidazole derivatives as modulators of tnf activity |
| CA3019026A1 (en) | 2016-04-01 | 2017-10-05 | Ucb Biopharma Sprl | Fused pentacyclic imidazole derivatives as modulators of tnf activity |
| EP3436460B1 (en) | 2016-04-01 | 2021-08-18 | UCB Biopharma SRL | Fused pentacyclic imidazole derivatives as modulators of tnf activity |
| MA44629A (fr) * | 2016-04-04 | 2021-03-24 | Chemocentryx Inc | Antagonistes de c5ar solubles |
| WO2018167176A1 (en) | 2017-03-15 | 2018-09-20 | Ucb Biopharma Sprl | Fused pentacyclic imidazole derivatives as modulators of tnf activity |
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| PL4073025T3 (pl) | 2019-12-13 | 2024-09-16 | Inspirna, Inc. | Sole metali i ich zastosowania |
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| CN101248048B (zh) * | 2005-06-27 | 2013-08-28 | 埃克塞利希斯专利有限责任公司 | 吡唑基lxr调节剂 |
| NZ564916A (en) * | 2005-06-27 | 2011-03-31 | Exelixis Inc | Imidazole based LXR modulators |
| KR20090094125A (ko) * | 2006-12-08 | 2009-09-03 | 엑셀리시스, 인코포레이티드 | Ｌｘｒ 및 ｆｘｒ 조절자 |
| EP2139847A1 (en) * | 2007-03-05 | 2010-01-06 | Yissum Research Development Company, of The Hebrew University of Jerusalem | Novel quinonoid derivatives of cannabinoids and their use in the treatment of malignancies |
| SI2435410T1 (sl) | 2009-05-28 | 2017-06-30 | Bristol-Myers Squibb Company | Lxr modulatorji |
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- 2012-03-23 TW TW101110267A patent/TW201242953A/zh unknown
- 2012-03-23 AR ARP120100996A patent/AR088728A1/es not_active Application Discontinuation
- 2012-03-26 WO PCT/US2012/030499 patent/WO2012135082A1/en not_active Ceased
- 2012-03-26 US US14/006,980 patent/US8901106B2/en active Active
- 2012-03-26 JP JP2014501296A patent/JP2014510110A/ja active Pending
- 2012-03-26 CN CN201280014836.6A patent/CN103443082B/zh not_active Expired - Fee Related
- 2012-03-26 ES ES12711739.8T patent/ES2548050T3/es active Active
- 2012-03-26 EP EP12711739.8A patent/EP2688871B1/en not_active Not-in-force
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| JP2014510110A (ja) | 2014-04-24 |
| AR088728A1 (es) | 2014-07-02 |
| US8901106B2 (en) | 2014-12-02 |
| EP2688871B1 (en) | 2015-08-26 |
| US20140018321A1 (en) | 2014-01-16 |
| CN103443082A (zh) | 2013-12-11 |
| WO2012135082A1 (en) | 2012-10-04 |
| EP2688871A1 (en) | 2014-01-29 |
| CN103443082B (zh) | 2015-11-25 |
| TW201242953A (en) | 2012-11-01 |
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