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
- 238000001144 powder X-ray diffraction data Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000002411 thermogravimetry Methods 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000011877 solvent mixture Substances 0.000 description 5
- 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
- 210000002381 plasma Anatomy 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 108010079943 Pentagastrin Proteins 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 239000012296 anti-solvent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 3
- 229960000444 pentagastrin Drugs 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 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
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 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
- 239000000725 suspension Substances 0.000 description 2
- 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
- 102100022594 ATP-binding cassette sub-family G member 1 Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 101150017419 CLTB gene Proteins 0.000 description 1
- 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
- 241000699800 Cricetinae Species 0.000 description 1
- 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
- 108010001831 LDL receptors Proteins 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 108010090314 Member 1 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 238000005388 cross polarization Methods 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 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
- 230000029142 excretion Effects 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 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
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 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
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000000547 structure data Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 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
- 238000011680 zucker rat Methods 0.000 description 1
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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P9/10—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 |
|---|---|---|---|---|
| EP3441390A1 (en) | 2012-03-02 | 2019-02-13 | Ralexar Therapeutics, Inc. | Liver x receptor (lxr) modulators for the treatment of dermal diseases, disorders and conditions |
| ES2765573T3 (es) | 2012-08-13 | 2020-06-09 | Univ Rockefeller | Tratamiento y diagnóstico de melanoma |
| EP2968275B1 (en) * | 2013-03-15 | 2017-11-29 | Bristol-Myers Squibb Company | Lxr modulators |
| AU2014315280B2 (en) | 2013-09-04 | 2019-01-24 | Ellora Therapeutics, Inc. | Liver X receptor (LXR) modulators |
| SG11201601644RA (en) | 2013-09-04 | 2016-04-28 | Alexar Therapeutics Inc | Liver x receptor (lxr) modulators |
| EP3091970B1 (en) | 2014-01-10 | 2020-10-28 | Rgenix, Inc. | Lxr agonists and uses thereof |
| PE20170693A1 (es) | 2014-10-03 | 2017-06-13 | Ucb Biopharma Sprl | Derivados de imidazol pentaciclicos fusionados |
| US11648220B2 (en) | 2016-01-11 | 2023-05-16 | The Rockefeller University | Methods for the treatment of myeloid derived suppressor cells related disorders |
| US10793578B2 (en) | 2016-04-01 | 2020-10-06 | UCB Biopharma SRL | Fused pentacyclic imidazole derivatives as modulators of TNF activity |
| US10766906B2 (en) | 2016-04-01 | 2020-09-08 | UCB Biopharma SRL | Fused hexacyclic imidazole derivatives as modulators of TNF activity |
| EA201892142A1 (ru) | 2016-04-01 | 2019-04-30 | Юсб Байофарма Спрл | Конденсированные пентациклические производные имидазола в качестве модуляторов активности tnf |
| EP3436459B1 (en) | 2016-04-01 | 2021-08-25 | UCB Biopharma SRL | Fused pentacyclic imidazole derivatives as modulators of tnf activity |
| WO2017176620A2 (en) | 2016-04-04 | 2017-10-12 | Chemocentryx, Inc. | SOLUBLE C5aR ANTAGONISTS |
| EP3596078B1 (en) | 2017-03-15 | 2023-04-12 | UCB Biopharma SRL | Fused pentacyclic imidazole derivatives as modulators of tnf activity |
| AU2018373028A1 (en) | 2017-11-21 | 2020-04-30 | Inspirna, Inc. | Polymorphs and uses thereof |
| EP4073025B1 (en) | 2019-12-13 | 2024-03-27 | Inspirna, Inc. | Metal salts and uses thereof |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| US4444784A (en) | 1980-08-05 | 1984-04-24 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| MX7065E (es) | 1980-06-06 | 1987-04-10 | Sankyo Co | Un procedimiento microbiologico para preparar derivados de ml-236b |
| WO1984002131A1 (fr) | 1982-11-22 | 1984-06-07 | Sandoz Ag | Produits analogues de mevalolactone et leurs derives, leurs procedes de production, compositions pharmaceutiques les contenant ainsi que leur utilisation en tant que produits pharmaceutiques |
| US5354772A (en) | 1982-11-22 | 1994-10-11 | Sandoz Pharm. Corp. | Indole analogs of mevalonolactone and derivatives thereof |
| FI94339C (fi) | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| US5177080A (en) | 1990-12-14 | 1993-01-05 | Bayer Aktiengesellschaft | Substituted pyridyl-dihydroxy-heptenoic acid and its salts |
| ATE215601T1 (de) | 1991-09-17 | 2002-04-15 | Salk Inst For Biological Studi | Rezeptoren der steroid/thyroid superfamilie von rezeptoren |
| AU5928898A (en) | 1997-01-24 | 1998-08-18 | Regents Of The University Of California, The | Use of fxr, pparalpha and lxralpha activators to restore barrier function, promote epidermal differentiation and inhibit proliferation |
| US5767134A (en) * | 1997-05-15 | 1998-06-16 | Vion Pharmaceuticals, Inc. | Prodrug forms of ribonucleotide reductase inhibitors 3-AP and 3-AMP |
| EP1115853A2 (en) | 1998-09-23 | 2001-07-18 | Ludmila Solomin | Analysis of ligand activated nuclear receptors in vivo |
| ES2326850T3 (es) | 1998-12-23 | 2009-10-20 | Glaxo Group Limited | Ensayos para ligandos de receptores nucleares. |
| US6071955A (en) | 1999-02-25 | 2000-06-06 | The Regents Of The University Of California | FXR, PPARA and LXRA activators to treat acne/acneiform conditions |
| US6316503B1 (en) | 1999-03-15 | 2001-11-13 | Tularik Inc. | LXR modulators |
| WO2000057915A1 (en) | 1999-03-26 | 2000-10-05 | City Of Hope | Method of affecting cholesterol catabolism using nuclear bile acid receptor |
| ATE422545T1 (de) | 1999-06-18 | 2009-02-15 | Cv Therapeutics Inc | Regulierung mittels atp binding cassette transporter proteins abc1 |
| EP1212065A4 (en) | 1999-07-08 | 2004-02-11 | Tularik Inc | COMPILATIONS AND METHODS FOR INCREASING THE HDL CHOLESTEROL LEVEL |
| WO2001060818A1 (en) | 2000-02-14 | 2001-08-23 | Tularik Inc. | Lxr modulators |
| WO2001082917A2 (en) | 2000-05-03 | 2001-11-08 | Tularik Inc. | Treatment of hypertriglyceridemia and other conditions using lxr modulators |
| US6924311B2 (en) | 2001-10-17 | 2005-08-02 | X-Ceptor Therapeutics, Inc. | Methods for affecting various diseases utilizing LXR compounds |
| DE602004014806D1 (de) * | 2003-10-08 | 2008-08-14 | Smithkline Beecham Corp | Triphenylethyleneverbindungen als selektive modulatoren des östrogenrezeptors |
| WO2006066070A2 (en) * | 2004-12-17 | 2006-06-22 | Nps Pharmaceuticals, Inc. | Prodrug constructs of pyrimidinone compounds as calcilytics |
| WO2007002563A1 (en) * | 2005-06-27 | 2007-01-04 | Exelixis, Inc. | Imidazole based lxr modulators |
| CN101248049B (zh) * | 2005-06-27 | 2013-08-28 | 埃克塞利希斯专利有限责任公司 | 咪唑类lxr调节剂 |
| WO2008073825A1 (en) * | 2006-12-08 | 2008-06-19 | Exelixis, Inc. | Lxr and fxr modulators |
| US20100152238A1 (en) * | 2007-03-05 | 2010-06-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Novel quinonoid derivatives of cannabinoids and their use in the treatment of malignancies |
| HRP20170194T1 (hr) | 2009-05-28 | 2017-05-19 | Exelixis Patent Company Llc | Lxr modulatori |
-
2012
- 2012-03-23 AR ARP120100996A patent/AR088728A1/es not_active Application Discontinuation
- 2012-03-23 TW TW101110267A patent/TW201242953A/zh unknown
- 2012-03-26 WO PCT/US2012/030499 patent/WO2012135082A1/en not_active Ceased
- 2012-03-26 JP JP2014501296A patent/JP2014510110A/ja active Pending
- 2012-03-26 US US14/006,980 patent/US8901106B2/en active Active
- 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
Also Published As
| Publication number | Publication date |
|---|---|
| AR088728A1 (es) | 2014-07-02 |
| CN103443082B (zh) | 2015-11-25 |
| WO2012135082A1 (en) | 2012-10-04 |
| US20140018321A1 (en) | 2014-01-16 |
| EP2688871B1 (en) | 2015-08-26 |
| US8901106B2 (en) | 2014-12-02 |
| CN103443082A (zh) | 2013-12-11 |
| JP2014510110A (ja) | 2014-04-24 |
| TW201242953A (en) | 2012-11-01 |
| EP2688871A1 (en) | 2014-01-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017284702B2 (en) | Pyrrolopyrimidine crystal for preparing JAK inhibitor | |
| US20220127262A1 (en) | Crystalline form of a cdk inhibitor | |
| JP2026001041A (ja) | ２－［３－［４－アミノ－３－（２－フルオロ－４－フェノキシ－フェニル）－１ｈ－ピラゾロ［３，４－ｄ］ピリミジン－１－イル］ピペリジン－１－カルボニル］－４－メチル－４－［４－（オキセタン－３－イル）ピペラジン－１－イル］ペンタ－２－エンニトリルの結晶形態 | |
| CN103550159A (zh) | 盐酸苯达莫司汀固体形式 | |
| EA015677B1 (ru) | СОЛИ И КРИСТАЛЛИЧЕСКИЕ ФОРМЫ 2-МЕТИЛ-2-[4-(3-МЕТИЛ-2-ОКСО-8-ХИНОЛИН-3-ИЛ-2,3-ДИГИДРОИМИДАЗО[4,5-c]ХИНОЛИН-1-ИЛ)ФЕНИЛ]ПРОПИОНИТРИЛА | |
| US8372988B2 (en) | Crystalline forms of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethyl-amine | |
| US20090076272A1 (en) | Polymorphs of eszopiclone malate | |
| US20250163055A1 (en) | Polymorph of jak tyrosine kinase inhibitor and preparation method therefor | |
| WO2019228485A1 (zh) | 一种甲磺酸乐伐替尼新晶型及其制备方法 | |
| CN102702041B (zh) | 阿戈美拉汀苯磺酸类复合物及其制备方法 | |
| KR20030036659A (ko) | 잘레플론의 동질이상체 및 이의 제조 방법 | |
| Li et al. | Versatile solid forms of boscalid: insight into the crystal structures and phase transformations | |
| CN114369093A (zh) | 化合物的盐及其晶型 | |
| US11466008B2 (en) | Co-crystals of neflamapimod (VX-745) | |
| US8691981B2 (en) | Crystalline forms of (S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide | |
| BRPI0711508A2 (pt) | formas cristalinas a,b,c, e x , processo para preparar as formas cristalinas a,b,c,e x formulação farmacêutica, uso das formas a,b,c, e x, e processo para preparar a forma amorfa de cloridrato de (r) -5-(2-aminoetil) - 1 - (6,8 -difluorocroman -3- il), - 1,3-diidroimidazol - 2-tiona | |
| Kalavalapudi et al. | Serendipitous discovery of a novel polymorph of an immunosuppressant drug azathioprine: phase transformation, solubility, dissolution and stability study | |
| BR112019003949B1 (pt) | Sal de (r)-(1-metilpirrolidina-3-il)metil(3-cloro-4- fluoro-[1,1-bifenil] -2-il)carbamato inovador e uma forma cristalina dos mesmos | |
| EP4504721A1 (en) | Birinapant polymorph h | |
| TW202319050A (zh) | 氮雜螺環化合物 | |
| Araya et al. | The effect of solution environment and the electrostatic factor on the crystallisation of desmotropes of irbesartan | |
| KR20220124752A (ko) | 2-[3-[4-아미노-3-(2-플루오로-4-페녹시-페닐)-1h-피라졸로[3,4-d]피리미딘-1-일]피페리딘-1-카르보닐]-4,4-디메틸펜트-2-엔니트릴의 결정 형태 | |
| HK40058992A (en) | Crystalline form of a cdk inhibitor | |
| EA044645B1 (ru) | Способ получения апиксабана | |
| CN119285594A (zh) | 7-氨基苯并吡喃酮或7-氨基喹啉酮类化合物及其应用 |