ES2887008T3 - Formas cristalinas y de sal de compuestos agonistas del PPAR - Google Patents
Formas cristalinas y de sal de compuestos agonistas del PPAR Download PDFInfo
- Publication number
- ES2887008T3 ES2887008T3 ES17787774T ES17787774T ES2887008T3 ES 2887008 T3 ES2887008 T3 ES 2887008T3 ES 17787774 T ES17787774 T ES 17787774T ES 17787774 T ES17787774 T ES 17787774T ES 2887008 T3 ES2887008 T3 ES 2887008T3
- Authority
- ES
- Spain
- Prior art keywords
- disease
- compound
- syndrome
- hemisulfate
- muscle
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 95
- 150000003839 salts Chemical group 0.000 title claims abstract description 56
- 229940126033 PPAR agonist Drugs 0.000 title description 2
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 41
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 210000003205 muscle Anatomy 0.000 claims description 13
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 10
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 8
- 208000030159 metabolic disease Diseases 0.000 claims description 8
- 208000029578 Muscle disease Diseases 0.000 claims description 7
- 201000009338 distal myopathy Diseases 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 230000005855 radiation Effects 0.000 claims description 7
- 208000019553 vascular disease Diseases 0.000 claims description 7
- 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 claims description 6
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 6
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 6
- 208000004350 Strabismus Diseases 0.000 claims description 6
- 208000002780 macular degeneration Diseases 0.000 claims description 6
- 208000012268 mitochondrial disease Diseases 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 5
- 208000016192 Demyelinating disease Diseases 0.000 claims description 5
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
- 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 claims description 5
- 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 claims description 5
- 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 208000033626 Renal failure acute Diseases 0.000 claims description 5
- 201000011040 acute kidney failure Diseases 0.000 claims description 5
- 230000007812 deficiency Effects 0.000 claims description 5
- 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 5
- 239000000835 fiber Substances 0.000 claims description 5
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 5
- 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 claims description 4
- 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 claims description 4
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 4
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010022562 Intermittent claudication Diseases 0.000 claims description 4
- 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims description 4
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 claims description 4
- 206010049565 Muscle fatigue Diseases 0.000 claims description 4
- 201000009623 Myopathy Diseases 0.000 claims description 4
- 208000014245 Ocular vascular disease Diseases 0.000 claims description 4
- 208000013234 Pearson syndrome Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 208000016097 disease of metabolism Diseases 0.000 claims description 4
- 208000006750 hematuria Diseases 0.000 claims description 4
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 4
- 208000017169 kidney disease Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 201000000585 muscular atrophy Diseases 0.000 claims description 4
- 201000008383 nephritis Diseases 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 208000028048 Accommodation disease Diseases 0.000 claims description 3
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 3
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 3
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 3
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
- 208000035177 MELAS Diseases 0.000 claims description 3
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 3
- 208000010428 Muscle Weakness Diseases 0.000 claims description 3
- 206010028372 Muscular weakness Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 3
- 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 3
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 3
- 230000001272 neurogenic effect Effects 0.000 claims description 3
- 230000008555 neuronal activation Effects 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 206010030875 ophthalmoplegia Diseases 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 235000019192 riboflavin Nutrition 0.000 claims description 3
- 229960002477 riboflavin Drugs 0.000 claims description 3
- 239000002151 riboflavin Substances 0.000 claims description 3
- 208000001392 short chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 201000010866 very long chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 3
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 2
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 2
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000012904 Bartter disease Diseases 0.000 claims description 2
- 208000010062 Bartter syndrome Diseases 0.000 claims description 2
- 208000006304 Bethlem myopathy Diseases 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- 208000015374 Central core disease Diseases 0.000 claims description 2
- 201000003728 Centronuclear myopathy Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 208000035902 Critical illness myopathy Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 208000002249 Diabetes Complications Diseases 0.000 claims description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
- 206010012655 Diabetic complications Diseases 0.000 claims description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 208000001692 Esotropia Diseases 0.000 claims description 2
- 201000005538 Exotropia Diseases 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 2
- 208000010412 Glaucoma Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 2
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 2
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims description 2
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims description 2
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 101000841267 Homo sapiens Long chain 3-hydroxyacyl-CoA dehydrogenase Proteins 0.000 claims description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 2
- 206010020675 Hypermetropia Diseases 0.000 claims description 2
- 206010020961 Hypocholesterolaemia Diseases 0.000 claims description 2
- 208000034767 Hypoproteinaemia Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 206010022489 Insulin Resistance Diseases 0.000 claims description 2
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 claims description 2
- 102100029107 Long chain 3-hydroxyacyl-CoA dehydrogenase Human genes 0.000 claims description 2
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims description 2
- 108700000232 Medium chain acyl CoA dehydrogenase deficiency Proteins 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
- 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 2
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 2
- 206010028289 Muscle atrophy Diseases 0.000 claims description 2
- 208000021642 Muscular disease Diseases 0.000 claims description 2
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 2
- 208000034965 Nemaline Myopathies Diseases 0.000 claims description 2
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 2
- 206010029323 Neuromyopathy Diseases 0.000 claims description 2
- 208000004286 Osteochondrodysplasias Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000010886 Peripheral nerve injury Diseases 0.000 claims description 2
- 206010036802 Progressive external ophthalmoplegia Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000037111 Retinal Hemorrhage Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 206010038926 Retinopathy hypertensive Diseases 0.000 claims description 2
- 208000018675 Schwartz-Jampel syndrome Diseases 0.000 claims description 2
- 201000003222 Schwartz-Jampel syndrome 1 Diseases 0.000 claims description 2
- 108010052164 Sodium Channels Proteins 0.000 claims description 2
- 102000018674 Sodium Channels Human genes 0.000 claims description 2
- 208000027073 Stargardt disease Diseases 0.000 claims description 2
- 206010066218 Stress Urinary Incontinence Diseases 0.000 claims description 2
- 208000032978 Structural Congenital Myopathies Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 206010054880 Vascular insufficiency Diseases 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 206010000496 acne Diseases 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 206010002537 anisometropia Diseases 0.000 claims description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000009310 astigmatism Diseases 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 201000007303 central core myopathy Diseases 0.000 claims description 2
- 206010008129 cerebral palsy Diseases 0.000 claims description 2
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 206010010121 compartment syndrome Diseases 0.000 claims description 2
- 230000007850 degeneration Effects 0.000 claims description 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 2
- 208000007345 glycogen storage disease Diseases 0.000 claims description 2
- 201000004502 glycogen storage disease II Diseases 0.000 claims description 2
- 208000014391 hyaline body myopathy Diseases 0.000 claims description 2
- 201000001421 hyperglycemia Diseases 0.000 claims description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 2
- 201000008980 hyperinsulinism Diseases 0.000 claims description 2
- 201000006318 hyperopia Diseases 0.000 claims description 2
- 230000004305 hyperopia Effects 0.000 claims description 2
- 230000001631 hypertensive effect Effects 0.000 claims description 2
- 201000001948 hypertensive retinopathy Diseases 0.000 claims description 2
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 2
- 201000008319 inclusion body myositis Diseases 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 208000006443 lactic acidosis Diseases 0.000 claims description 2
- 210000002429 large intestine Anatomy 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 claims description 2
- 150000004682 monohydrates Chemical class 0.000 claims description 2
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 2
- 230000020763 muscle atrophy Effects 0.000 claims description 2
- 208000029372 muscular lipidosis Diseases 0.000 claims description 2
- 206010028417 myasthenia gravis Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 208000001491 myopia Diseases 0.000 claims description 2
- 230000004379 myopia Effects 0.000 claims description 2
- 201000009925 nephrosclerosis Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 201000001119 neuropathy Diseases 0.000 claims description 2
- 230000007823 neuropathy Effects 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000001696 pelvic girdle Anatomy 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 230000002085 persistent effect Effects 0.000 claims description 2
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 2
- 201000010041 presbyopia Diseases 0.000 claims description 2
- 230000000750 progressive effect Effects 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 230000000306 recurrent effect Effects 0.000 claims description 2
- 208000001076 sarcopenia Diseases 0.000 claims description 2
- 210000002832 shoulder Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- 231100000399 thyrotoxic Toxicity 0.000 claims description 2
- 230000001897 thyrotoxic effect Effects 0.000 claims description 2
- 208000023577 vascular insufficiency disease Diseases 0.000 claims description 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010020740 Hyperproteinaemia Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000029091 Refraction disease Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 210000000748 cardiovascular system Anatomy 0.000 claims 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 208000010706 fatty liver disease Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 201000005296 lung carcinoma Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 claims 1
- 201000001514 prostate carcinoma Diseases 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 210000000658 ulnar nerve Anatomy 0.000 claims 1
- 229940126062 Compound A Drugs 0.000 description 128
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 128
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- 238000000034 method Methods 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 9
- 238000012216 screening Methods 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 108020001756 ligand binding domains Proteins 0.000 description 6
- 229960003194 meglumine Drugs 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- -1 5-methyl-2-(4-(trifluoromethyl)phenyl)-1H-imidazol-1-yl Chemical group 0.000 description 5
- 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 238000000113 differential scanning calorimetry Methods 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 201000006938 muscular dystrophy Diseases 0.000 description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 5
- 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- UKKFYSLMACHPAJ-UHFFFAOYSA-N COC1=C(CN2C(C)=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C(C)=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 UKKFYSLMACHPAJ-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- SWKPKONEIZGROQ-UHFFFAOYSA-N 4-trifluoromethylbenzoic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C=C1 SWKPKONEIZGROQ-UHFFFAOYSA-N 0.000 description 2
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- QZWQLFCJTVVBIU-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C(F)(F)F Chemical compound CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C(F)(F)F QZWQLFCJTVVBIU-UHFFFAOYSA-N 0.000 description 2
- OMCDNQOMTAHLDT-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(C=CC=C1)O)C=1C=NC(=CC=1)C(F)(F)F Chemical compound CC1=CN=C(N1CC1=C(C=CC=C1)O)C=1C=NC(=CC=1)C(F)(F)F OMCDNQOMTAHLDT-UHFFFAOYSA-N 0.000 description 2
- WNDPXYAVRBQZAL-UHFFFAOYSA-N COC1=C(CN2C(=NC=C2C)C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C(=NC=C2C)C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 WNDPXYAVRBQZAL-UHFFFAOYSA-N 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 206010012559 Developmental delay Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- KEQLCUZKLBSQTD-MRVPVSSYSA-N ethyl (3R)-6-bromo-3-methylhexanoate Chemical compound BrCCC[C@H](CC(=O)OCC)C KEQLCUZKLBSQTD-MRVPVSSYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- ADENVXCOJGUNQE-UHFFFAOYSA-N n-prop-2-ynyl-4-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC=C(C(=O)NCC#C)C=C1 ADENVXCOJGUNQE-UHFFFAOYSA-N 0.000 description 2
- SCMZYNODBBJLAB-UHFFFAOYSA-N n-prop-2-ynyl-6-(trifluoromethyl)pyridine-3-carboxamide Chemical compound FC(F)(F)C1=CC=C(C(=O)NCC#C)C=N1 SCMZYNODBBJLAB-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 102000006255 nuclear receptors Human genes 0.000 description 2
- 108020004017 nuclear receptors Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001144 powder X-ray diffraction data Methods 0.000 description 2
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002076 thermal analysis method Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 1
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 1
- QCSAGIPMTZIRPT-UHFFFAOYSA-N 5-(5-methyl-1H-imidazol-2-yl)-2-(trifluoromethyl)pyridine Chemical compound CC1=CN=C(N1)C=1C=NC(=CC=1)C(F)(F)F QCSAGIPMTZIRPT-UHFFFAOYSA-N 0.000 description 1
- JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 description 1
- 108010001058 Acyl-CoA Dehydrogenase Proteins 0.000 description 1
- 102000002735 Acyl-CoA Dehydrogenase Human genes 0.000 description 1
- 208000036022 Alpers' disease Diseases 0.000 description 1
- 201000006935 Becker muscular dystrophy Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010068197 Butyryl-CoA Dehydrogenase Proteins 0.000 description 1
- KUAHQEKMSUCTHL-UHFFFAOYSA-N CC#CCNC(c1ccc(C(F)(F)F)cc1)=O Chemical compound CC#CCNC(c1ccc(C(F)(F)F)cc1)=O KUAHQEKMSUCTHL-UHFFFAOYSA-N 0.000 description 1
- JTZDJRDRTSBLPH-UHFFFAOYSA-N CC(CC1)C(C(F)(F)F)=CC=C1c1ncc(C)[n]1Cc1ccccc1[N+]([O-])=O Chemical compound CC(CC1)C(C(F)(F)F)=CC=C1c1ncc(C)[n]1Cc1ccccc1[N+]([O-])=O JTZDJRDRTSBLPH-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 101710147349 Carnitine transporter Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000009564 MELAS Syndrome Diseases 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- 102100026784 Myelin proteolipid protein Human genes 0.000 description 1
- 102000034570 NR1 subfamily Human genes 0.000 description 1
- 108020001305 NR1 subfamily Proteins 0.000 description 1
- 201000009110 Oculopharyngeal muscular dystrophy Diseases 0.000 description 1
- 229910020667 PBr3 Inorganic materials 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 description 1
- 241000932075 Priacanthus hamrur Species 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 108700017825 Short chain Acyl CoA dehydrogenase deficiency Proteins 0.000 description 1
- 206010059790 Ulnar nerve palsy Diseases 0.000 description 1
- SJZAPSHKTOTRBQ-UHFFFAOYSA-N [dimethylamino(triazolo[4,5-b]pyridin-1-yl)methylidene]-dimethylazanium Chemical compound C1=CC=C2[N+](=C(N(C)C)N(C)C)N=NC2=N1 SJZAPSHKTOTRBQ-UHFFFAOYSA-N 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- SSJQOTXWMLWHOK-MRVPVSSYSA-N ethyl (3R)-6-hydroxy-3-methylhexanoate Chemical compound OCCC[C@H](CC(=O)OCC)C SSJQOTXWMLWHOK-MRVPVSSYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000029498 hypoalphalipoproteinemia Diseases 0.000 description 1
- 201000001451 hypomyelinating leukodystrophy Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000009756 muscle regeneration Effects 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 230000003274 myotonic effect Effects 0.000 description 1
- REPVNSJSTLRQEQ-UHFFFAOYSA-N n,n-dimethylacetamide;n,n-dimethylformamide Chemical compound CN(C)C=O.CN(C)C(C)=O REPVNSJSTLRQEQ-UHFFFAOYSA-N 0.000 description 1
- OXCREIAATRYJNU-UHFFFAOYSA-N n-benzyl-2-methoxyaniline Chemical compound COC1=CC=CC=C1NCC1=CC=CC=C1 OXCREIAATRYJNU-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 208000008795 neuromyelitis optica Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000006611 pharmacological activation Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 208000036722 ulnar neuropathy Diseases 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
Classifications
-
- 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
-
- 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
- A61K31/33—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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/60—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662404474P | 2016-10-05 | 2016-10-05 | |
| PCT/US2017/055403 WO2018067860A1 (en) | 2016-10-05 | 2017-10-05 | Crystalline and salt forms of ppar agonist compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2887008T3 true ES2887008T3 (es) | 2021-12-21 |
Family
ID=60153508
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17787774T Active ES2887008T3 (es) | 2016-10-05 | 2017-10-05 | Formas cristalinas y de sal de compuestos agonistas del PPAR |
Country Status (30)
| Country | Link |
|---|---|
| US (3) | US10927094B2 (https=) |
| EP (1) | EP3523283B1 (https=) |
| JP (1) | JP7017563B2 (https=) |
| KR (1) | KR20190057129A (https=) |
| CN (1) | CN109843857B (https=) |
| AU (1) | AU2017340763B2 (https=) |
| CA (1) | CA3036587A1 (https=) |
| CO (1) | CO2019003162A2 (https=) |
| CY (1) | CY1124655T1 (https=) |
| DK (1) | DK3523283T3 (https=) |
| ES (1) | ES2887008T3 (https=) |
| HR (1) | HRP20211341T1 (https=) |
| HU (1) | HUE055678T2 (https=) |
| IL (1) | IL265730B (https=) |
| JO (1) | JOP20190039B1 (https=) |
| LT (1) | LT3523283T (https=) |
| MA (1) | MA46460A (https=) |
| MX (1) | MX385973B (https=) |
| MY (1) | MY202008A (https=) |
| PH (1) | PH12019500727A1 (https=) |
| PL (1) | PL3523283T3 (https=) |
| PT (1) | PT3523283T (https=) |
| RS (1) | RS62245B1 (https=) |
| RU (1) | RU2759724C2 (https=) |
| SG (1) | SG11201901995TA (https=) |
| SI (1) | SI3523283T1 (https=) |
| TW (1) | TWI769182B (https=) |
| UA (1) | UA124770C2 (https=) |
| WO (1) | WO2018067860A1 (https=) |
| ZA (1) | ZA201901744B (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1888548E (pt) | 2005-05-26 | 2012-10-30 | Neuron Systems Inc | Derivado de quinolina para o tratamento de doenças da retina |
| WO2011072141A1 (en) | 2009-12-11 | 2011-06-16 | Neuron Systems, Inc. | Compositions and methods for the treatment of macular degeneration |
| CA2898631C (en) | 2013-01-23 | 2023-06-13 | Aldeyra Therapeutics, Inc. | Toxic aldehyde related diseases and treatment |
| CN118724806A (zh) | 2015-08-21 | 2024-10-01 | 奥尔德拉医疗公司 | 氘化化合物和其用途 |
| KR102667386B1 (ko) * | 2015-10-07 | 2024-05-21 | 미토브리지, 인크. | Ppar 효능제, 화합물, 제약 조성물, 및 그의 사용 방법 |
| PL3523283T3 (pl) | 2016-10-05 | 2021-12-13 | Mitobridge, Inc. | Postacie krystaliczne i postacie soli związków stanowiących agonistów ppar |
| JP7311162B2 (ja) | 2017-10-10 | 2023-07-19 | アルデイラ セラピューティクス， インコーポレイテッド | 炎症性障害の処置 |
| WO2020033344A1 (en) * | 2018-08-06 | 2020-02-13 | Aldeyra Therapeutics, Inc. | Polymorphic compounds and uses thereof |
| JP7397491B2 (ja) * | 2018-10-23 | 2023-12-13 | 国立研究開発法人科学技術振興機構 | ＰＰＡＲδ活性化剤 |
| CN113784954A (zh) | 2019-05-02 | 2021-12-10 | 奥尔德拉医疗公司 | 多晶型化合物和其用途 |
| US12098132B2 (en) | 2019-05-02 | 2024-09-24 | Aldeyra Therapeutics, Inc. | Process for preparation of aldehyde scavenger and intermediates |
| CA3175856A1 (en) | 2020-05-13 | 2021-11-18 | Todd Brady | Pharmaceutical formulations and uses thereof |
| WO2022256540A1 (en) | 2021-06-02 | 2022-12-08 | Astellas Pharma Inc. | Methods of use of ppar agonist compounds and pharmaceutical compositions thereof |
| WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
| WO2025207099A1 (en) * | 2024-03-28 | 2025-10-02 | Astellas Pharma Inc. | Ppar-delta inhibitors for preventing post-operative atrial fibrillation |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7396850B2 (en) | 2003-01-06 | 2008-07-08 | Eli Lilly And Company | Pyrazole derivative as PPAR modulator |
| EP1671633A1 (en) * | 2004-12-17 | 2006-06-21 | Sanofi-Aventis Deutschland GmbH | Use of PPAR agonists for the treatment of congestive heart failure |
| AU2006210503B2 (en) * | 2005-02-03 | 2009-09-03 | Irm Llc | Compounds and compositions as PPAR modulators |
| CN101296892A (zh) * | 2005-09-07 | 2008-10-29 | 普莱希科公司 | Ppar活性化合物 |
| DE102006023336A1 (de) * | 2006-05-18 | 2007-11-22 | Merck Patent Gmbh | 1,5-Diphenyl-pyrazole II |
| FR2940289B1 (fr) | 2008-12-23 | 2014-09-12 | Biopharmed | Derives de la classe des hydroxyquinoleines aminees pour le traitement du cancer du pancreas |
| CN102727489A (zh) * | 2012-07-18 | 2012-10-17 | 西南大学 | 5-芳(杂环)亚甲基噻唑烷-2，4-二酮在制备ppar激动剂中的应用 |
| US20170305894A1 (en) * | 2014-10-08 | 2017-10-26 | Mitobridge, Inc. | Ppar agonists, compounds, pharmaceutical compositions, and methods of use thereof |
| KR102667386B1 (ko) | 2015-10-07 | 2024-05-21 | 미토브리지, 인크. | Ppar 효능제, 화합물, 제약 조성물, 및 그의 사용 방법 |
| BR112018069930B1 (pt) | 2016-04-13 | 2024-02-20 | Mitobridge, Inc | Compostos agonistas de ppar, uso dos mesmos e composição farmacêutica |
| BR112019005539A2 (pt) | 2016-10-05 | 2019-06-18 | Mitobridge, Inc. | métodos de tratamento de lesão renal aguda |
| PL3523283T3 (pl) | 2016-10-05 | 2021-12-13 | Mitobridge, Inc. | Postacie krystaliczne i postacie soli związków stanowiących agonistów ppar |
-
2017
- 2017-10-05 PL PL17787774T patent/PL3523283T3/pl unknown
- 2017-10-05 AU AU2017340763A patent/AU2017340763B2/en active Active
- 2017-10-05 MX MX2019003945A patent/MX385973B/es unknown
- 2017-10-05 US US16/334,746 patent/US10927094B2/en active Active
- 2017-10-05 CN CN201780062034.5A patent/CN109843857B/zh active Active
- 2017-10-05 PT PT177877743T patent/PT3523283T/pt unknown
- 2017-10-05 WO PCT/US2017/055403 patent/WO2018067860A1/en not_active Ceased
- 2017-10-05 JP JP2019518286A patent/JP7017563B2/ja active Active
- 2017-10-05 MA MA046460A patent/MA46460A/fr unknown
- 2017-10-05 SG SG11201901995TA patent/SG11201901995TA/en unknown
- 2017-10-05 DK DK17787774.3T patent/DK3523283T3/da active
- 2017-10-05 ES ES17787774T patent/ES2887008T3/es active Active
- 2017-10-05 MY MYPI2019001560A patent/MY202008A/en unknown
- 2017-10-05 LT LTEPPCT/US2017/055403T patent/LT3523283T/lt unknown
- 2017-10-05 HR HRP20211341TT patent/HRP20211341T1/hr unknown
- 2017-10-05 IL IL265730A patent/IL265730B/en unknown
- 2017-10-05 JO JOP/2019/0039A patent/JOP20190039B1/ar active
- 2017-10-05 SI SI201730879T patent/SI3523283T1/sl unknown
- 2017-10-05 HU HUE17787774A patent/HUE055678T2/hu unknown
- 2017-10-05 KR KR1020197012668A patent/KR20190057129A/ko not_active Ceased
- 2017-10-05 RU RU2019110736A patent/RU2759724C2/ru active
- 2017-10-05 CA CA3036587A patent/CA3036587A1/en active Pending
- 2017-10-05 EP EP17787774.3A patent/EP3523283B1/en active Active
- 2017-10-05 UA UAA201903678A patent/UA124770C2/uk unknown
- 2017-10-05 TW TW106134298A patent/TWI769182B/zh active
- 2017-10-05 RS RS20211042A patent/RS62245B1/sr unknown
-
2019
- 2019-03-20 ZA ZA2019/01744A patent/ZA201901744B/en unknown
- 2019-03-29 CO CONC2019/0003162A patent/CO2019003162A2/es unknown
- 2019-04-03 PH PH12019500727A patent/PH12019500727A1/en unknown
-
2021
- 2021-02-19 US US17/179,604 patent/US11530192B2/en active Active
- 2021-08-31 CY CY20211100775T patent/CY1124655T1/el unknown
-
2022
- 2022-12-16 US US18/082,847 patent/US11912681B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2887008T3 (es) | Formas cristalinas y de sal de compuestos agonistas del PPAR | |
| JP2022521825A (ja) | アンドロゲン受容体モジュレーター及びタンパク質分解誘導キメラリガンドとして使用するための方法 | |
| ES2988059T3 (es) | Agonistas de PPAR, compuestos, composiciones farmacéuticas y métodos de uso de los mismos | |
| US10130619B2 (en) | Amido thiadiazole derivatives as NADPH oxidase inhibitors | |
| CN118388473A (zh) | Fxr激动剂的固体形式 | |
| CN104837490B (zh) | 作为无义突变抑制子的嘧啶并[4，5‑b]喹啉‑4，5(3H，10H)‑二酮 | |
| ES2861503T3 (es) | Agonistas de PPAR, compuestos, composiciones farmacéuticas y métodos de uso de los mismos | |
| JP6462151B2 (ja) | グレリンｏ−アシルトランスフェラーゼ阻害剤 | |
| US20180092866A1 (en) | Substituted n-([1,1'-biphenyl]-3-yl)-[1,1'-biphenyl]-3-carboxamide analogs as inhibitors for beta-catenin/b-cell lymphoma 9 interactions | |
| KR101905295B1 (ko) | 나프티리딘디온 유도체 | |
| JP6560257B2 (ja) | ピリミド［４，５−ｂ］キノリン−４，５（３Ｈ，１０Ｈ）−ジオン誘導体 | |
| US20170057955A1 (en) | Pyridopyrimidinone Compounds for Modulating the Catalytic Activity of Histone Lysine Demethylases (KDMs) | |
| BR112020018642A2 (pt) | Composto da fórmula i, composição farmacêutica, método de tratamento de câncer em um sujeito em necessidade, método de eliminação de uma célula tumoral em um sujeito | |
| BR112019006030B1 (pt) | Formas cristalinas e de sal de compostos agonistas de ppar e seus usos | |
| HK40006508B (en) | Crystalline and salt forms of ppar agonist compounds | |
| HK40006508A (en) | Crystalline and salt forms of ppar agonist compounds |