KR102667386B1 - Ppar 효능제, 화합물, 제약 조성물, 및 그의 사용 방법 - Google Patents

Info

Publication number

KR102667386B1

KR102667386B1 KR1020217032197A KR20217032197A KR102667386B1 KR 102667386 B1 KR102667386 B1 KR 102667386B1 KR 1020217032197 A KR1020217032197 A KR 1020217032197A KR 20217032197 A KR20217032197 A KR 20217032197A KR 102667386 B1 KR102667386 B1 KR 102667386B1

Authority

KR

South Korea

Prior art keywords

methyl

disease

compound

mmol

pharmaceutically acceptable

Prior art date

2015-10-07

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

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 295
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 22
• 238000000034 method Methods 0.000 title description 28
• 239000000556 agonist Substances 0.000 title description 11
• 101150014691 PPARA gene Proteins 0.000 title 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 81
• 108010015181 PPAR delta Proteins 0.000 claims abstract description 69
• 201000010099 disease Diseases 0.000 claims abstract description 61
• 208000030159 metabolic disease Diseases 0.000 claims abstract description 10
• 208000029578 Muscle disease Diseases 0.000 claims abstract description 9
• 208000019553 vascular disease Diseases 0.000 claims abstract description 8
• 208000016192 Demyelinating disease Diseases 0.000 claims abstract description 6
• 150000003839 salts Chemical class 0.000 claims description 59
• 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims description 22
• 210000003205 muscle Anatomy 0.000 claims description 22
• 208000035475 disorder Diseases 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 20
• 150000002367 halogens Chemical class 0.000 claims description 20
• 201000006938 muscular dystrophy Diseases 0.000 claims description 15
• 210000001087 myotubule Anatomy 0.000 claims description 12
• 238000007254 oxidation reaction Methods 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 11
• 150000002431 hydrogen Chemical class 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 230000007812 deficiency Effects 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 9
• 230000003647 oxidation Effects 0.000 claims description 9
• 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 8
• 201000000639 Leber hereditary optic neuropathy Diseases 0.000 claims description 8
• 208000004350 Strabismus Diseases 0.000 claims description 8
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 8
• 230000000750 progressive effect Effects 0.000 claims description 8
• 208000009304 Acute Kidney Injury Diseases 0.000 claims description 7
• 208000033626 Renal failure acute Diseases 0.000 claims description 7
• 201000011040 acute kidney failure Diseases 0.000 claims description 7
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 6
• 208000035177 MELAS Diseases 0.000 claims description 6
• 201000009623 Myopathy Diseases 0.000 claims description 6
• 208000018262 Peripheral vascular disease Diseases 0.000 claims description 6
• 230000004054 inflammatory process Effects 0.000 claims description 6
• 208000017169 kidney disease Diseases 0.000 claims description 6
• 208000002780 macular degeneration Diseases 0.000 claims description 6
• 208000012268 mitochondrial disease Diseases 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 5
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 208000010428 Muscle Weakness Diseases 0.000 claims description 5
• 206010028372 Muscular weakness Diseases 0.000 claims description 5
• 208000036572 Myoclonic epilepsy Diseases 0.000 claims description 5
• 208000013234 Pearson syndrome Diseases 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 201000009028 early myoclonic encephalopathy Diseases 0.000 claims description 5
• 201000006417 multiple sclerosis Diseases 0.000 claims description 5
• 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 4
• 206010003591 Ataxia Diseases 0.000 claims description 4
• 108010068197 Butyryl-CoA Dehydrogenase Proteins 0.000 claims description 4
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
• 102000002666 Carnitine O-palmitoyltransferase Human genes 0.000 claims description 4
• 108010018424 Carnitine O-palmitoyltransferase Proteins 0.000 claims description 4
• 201000000915 Chronic Progressive External Ophthalmoplegia Diseases 0.000 claims description 4
• 206010022562 Intermittent claudication Diseases 0.000 claims description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
• 108010027062 Long-Chain Acyl-CoA Dehydrogenase Proteins 0.000 claims description 4
• 102000018653 Long-Chain Acyl-CoA Dehydrogenase Human genes 0.000 claims description 4
• 208000035172 MERRF Diseases 0.000 claims description 4
• 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 4
• 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 4
• 206010049565 Muscle fatigue Diseases 0.000 claims description 4
• 208000021642 Muscular disease Diseases 0.000 claims description 4
• 206010028980 Neoplasm Diseases 0.000 claims description 4
• 208000014245 Ocular vascular disease Diseases 0.000 claims description 4
• 206010033799 Paralysis Diseases 0.000 claims description 4
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 4
• 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 4
• 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 4
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 208000006750 hematuria Diseases 0.000 claims description 4
• 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 4
• 208000021156 intermittent vascular claudication Diseases 0.000 claims description 4
• 208000005548 medium chain acyl-CoA dehydrogenase deficiency Diseases 0.000 claims description 4
• 201000008383 nephritis Diseases 0.000 claims description 4
• 210000005036 nerve Anatomy 0.000 claims description 4
• 230000008555 neuronal activation Effects 0.000 claims description 4
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 4
• 206010030875 ophthalmoplegia Diseases 0.000 claims description 4
• 208000030613 peripheral artery disease Diseases 0.000 claims description 4
• 230000002093 peripheral effect Effects 0.000 claims description 4
• 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 3
• 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
• 208000001692 Esotropia Diseases 0.000 claims description 3
• 201000005538 Exotropia Diseases 0.000 claims description 3
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
• 206010028289 Muscle atrophy Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 208000016097 disease of metabolism Diseases 0.000 claims description 3
• 201000009338 distal myopathy Diseases 0.000 claims description 3
• 230000004064 dysfunction Effects 0.000 claims description 3
• 201000001421 hyperglycemia Diseases 0.000 claims description 3
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 3
• 208000006443 lactic acidosis Diseases 0.000 claims description 3
• 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 3
• 208000010125 myocardial infarction Diseases 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• 208000002874 Acne Vulgaris 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
• 200000000007 Arterial disease Diseases 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
• 206010006895 Cachexia Diseases 0.000 claims description 2
• 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
• 101710147349 Carnitine transporter Proteins 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
• 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 2
• 201000004624 Dermatitis Diseases 0.000 claims description 2
• 208000002249 Diabetes Complications 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
• 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
• 101000841267 Homo sapiens Long chain 3-hydroxyacyl-CoA dehydrogenase Proteins 0.000 claims description 2
• 206010020675 Hypermetropia Diseases 0.000 claims description 2
• 206010020740 Hyperproteinaemia Diseases 0.000 claims description 2
• 206010020961 Hypocholesterolaemia Diseases 0.000 claims description 2
• 208000034767 Hypoproteinaemia 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
• 208000002678 Mucopolysaccharidoses 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
• 206010033645 Pancreatitis Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 208000029107 Refractive and accommodative disease 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
• 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
• 208000007536 Thrombosis Diseases 0.000 claims description 2
• 206010044604 Trichiasis 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
• 230000002350 accommodative effect Effects 0.000 claims description 2
• 206010000496 acne Diseases 0.000 claims description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
• 206010002537 anisometropia 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
• 230000000747 cardiac effect Effects 0.000 claims description 2
• 210000000845 cartilage Anatomy 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
• 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
• 206010010121 compartment syndrome Diseases 0.000 claims description 2
• 230000007850 degeneration Effects 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
• 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
• 201000008319 inclusion body myositis Diseases 0.000 claims description 2
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
• 210000002429 large intestine Anatomy 0.000 claims description 2
• 230000003902 lesion Effects 0.000 claims description 2
• 208000036546 leukodystrophy Diseases 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 2
• 230000020763 muscle atrophy Effects 0.000 claims description 2
• 201000000585 muscular atrophy Diseases 0.000 claims description 2
• 208000029372 muscular lipidosis Diseases 0.000 claims description 2
• 206010028417 myasthenia gravis Diseases 0.000 claims description 2
• 208000001491 myopia Diseases 0.000 claims description 2
• 230000004379 myopia Effects 0.000 claims description 2
• 230000003274 myotonic effect 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
• 208000018360 neuromuscular disease Diseases 0.000 claims description 2
• 210000001672 ovary Anatomy 0.000 claims description 2
• 230000003836 peripheral circulation Effects 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
• 210000002307 prostate Anatomy 0.000 claims description 2
• 230000000306 recurrent effect Effects 0.000 claims description 2
• 235000019192 riboflavin Nutrition 0.000 claims description 2
• 229960002477 riboflavin Drugs 0.000 claims description 2
• 239000002151 riboflavin Substances 0.000 claims description 2
• 208000001076 sarcopenia Diseases 0.000 claims description 2
• 210000003491 skin Anatomy 0.000 claims description 2
• 230000009759 skin aging Effects 0.000 claims description 2
• 208000002320 spinal muscular atrophy Diseases 0.000 claims description 2
• 230000009885 systemic effect Effects 0.000 claims description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
• 231100000331 toxic Toxicity 0.000 claims description 2
• 230000002588 toxic effect Effects 0.000 claims description 2
• 208000023577 vascular insufficiency disease Diseases 0.000 claims description 2
• 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims 3
• 102000009030 Member 1 Subfamily D ATP Binding Cassette Transporter Human genes 0.000 claims 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims 2
• 150000002222 fluorine compounds Chemical class 0.000 claims 2
• 206010003210 Arteriosclerosis Diseases 0.000 claims 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
• 206010036802 Progressive external ophthalmoplegia Diseases 0.000 claims 1
• 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 claims 1
• 208000024799 Thyroid disease Diseases 0.000 claims 1
• 206010059790 Ulnar nerve palsy Diseases 0.000 claims 1
• 230000022159 cartilage development Effects 0.000 claims 1
• 210000001072 colon Anatomy 0.000 claims 1
• 208000033679 diabetic kidney disease Diseases 0.000 claims 1
• 201000008980 hyperinsulinism Diseases 0.000 claims 1
• 230000001272 neurogenic effect Effects 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 239000011574 phosphorus Substances 0.000 claims 1
• 208000021510 thyroid gland disease Diseases 0.000 claims 1
• 208000036722 ulnar neuropathy Diseases 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 45
• 238000011282 treatment Methods 0.000 abstract description 17
• 230000000694 effects Effects 0.000 abstract description 16
• 238000003786 synthesis reaction Methods 0.000 description 132
• 230000015572 biosynthetic process Effects 0.000 description 126
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
• 239000011541 reaction mixture Substances 0.000 description 104
• 238000005481 NMR spectroscopy Methods 0.000 description 99
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 97
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
• 239000000243 solution Substances 0.000 description 67
• 238000006243 chemical reaction Methods 0.000 description 60
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
• 238000004809 thin layer chromatography Methods 0.000 description 55
• QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 53
• 235000019439 ethyl acetate Nutrition 0.000 description 52
• 238000002474 experimental method Methods 0.000 description 51
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 45
• 239000012299 nitrogen atmosphere Substances 0.000 description 43
• -1 -OH Chemical group 0.000 description 42
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 42
• 239000011734 sodium Substances 0.000 description 41
• 239000007787 solid Substances 0.000 description 41
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 39
• 239000000284 extract Substances 0.000 description 34
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 26
• 238000004128 high performance liquid chromatography Methods 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• 241000699670 Mus sp. Species 0.000 description 25
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 25
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 23
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• KEQLCUZKLBSQTD-MRVPVSSYSA-N ethyl (3R)-6-bromo-3-methylhexanoate Chemical compound BrCCC[C@H](CC(=O)OCC)C KEQLCUZKLBSQTD-MRVPVSSYSA-N 0.000 description 16
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 15
• 238000010898 silica gel chromatography Methods 0.000 description 15
• CVKMFSAVYPAZTQ-UHFFFAOYSA-N 2-methylhexanoic acid Chemical compound CCCCC(C)C(O)=O CVKMFSAVYPAZTQ-UHFFFAOYSA-N 0.000 description 14
• 241001465754 Metazoa Species 0.000 description 14
• 210000004027 cell Anatomy 0.000 description 14
• 239000003814 drug Substances 0.000 description 14
• 238000005160 1H NMR spectroscopy Methods 0.000 description 13
• JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 13
• 239000003981 vehicle Substances 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• 206010016654 Fibrosis Diseases 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 238000010828 elution Methods 0.000 description 11
• 230000004761 fibrosis Effects 0.000 description 11
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000004093 cyano group Chemical group *C#N 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 206010028851 Necrosis Diseases 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 238000001990 intravenous administration Methods 0.000 description 7
• 230000008437 mitochondrial biogenesis Effects 0.000 description 7
• 238000010172 mouse model Methods 0.000 description 7
• 230000017074 necrotic cell death Effects 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 238000001228 spectrum Methods 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 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 description 6
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 6
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6
• 125000003118 aryl group Chemical group 0.000 description 6
• 230000006378 damage Effects 0.000 description 6
• 239000003480 eluent Substances 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 125000001153 fluoro group Chemical group F* 0.000 description 6
• 208000028867 ischemia Diseases 0.000 description 6
• NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 6
• 230000007935 neutral effect Effects 0.000 description 6
• 230000007170 pathology Effects 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 5
• 229940109239 creatinine Drugs 0.000 description 5
• 239000013058 crude material Substances 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 235000019441 ethanol Nutrition 0.000 description 5
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 5
• 229930195729 fatty acid Natural products 0.000 description 5
• 239000000194 fatty acid Substances 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 108020001756 ligand binding domains Proteins 0.000 description 5
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 5
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 5
• 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 5
• 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 5
• 210000003314 quadriceps muscle Anatomy 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• 238000007619 statistical method Methods 0.000 description 5
• 229940124597 therapeutic agent Drugs 0.000 description 5
• 238000001890 transfection Methods 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• GJWSUKYXUMVMGX-UHFFFAOYSA-N (+)-(R)-citronellic acid Natural products OC(=O)CC(C)CCC=C(C)C GJWSUKYXUMVMGX-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 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 4
• BMZRVOVNUMQTIN-UHFFFAOYSA-N Carbonyl Cyanide para-Trifluoromethoxyphenylhydrazone Chemical compound FC(F)(F)OC1=CC=C(NN=C(C#N)C#N)C=C1 BMZRVOVNUMQTIN-UHFFFAOYSA-N 0.000 description 4
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical group O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 4
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 4
• 206010061481 Renal injury Diseases 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• 230000017531 blood circulation Effects 0.000 description 4
• 230000000052 comparative effect Effects 0.000 description 4
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 4
• 229960002591 hydroxyproline Drugs 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 229960003194 meglumine Drugs 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 230000009756 muscle regeneration Effects 0.000 description 4
• 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 4
• 229910052757 nitrogen Inorganic materials 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• 230000008929 regeneration Effects 0.000 description 4
• 238000011069 regeneration method Methods 0.000 description 4
• 210000002027 skeletal muscle Anatomy 0.000 description 4
• 238000001356 surgical procedure Methods 0.000 description 4
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 4
• PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 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 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 208000029549 Muscle injury Diseases 0.000 description 3
• 229940122054 Peroxisome proliferator-activated receptor delta agonist Drugs 0.000 description 3
• 238000012311 Shapiro-Wilk normality test Methods 0.000 description 3
• 102000040945 Transcription factor Human genes 0.000 description 3
• 108091023040 Transcription factor Proteins 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 230000002354 daily effect Effects 0.000 description 3
• CSQGAUJUODHNIM-UHFFFAOYSA-N ethyl 6-bromo-2,2-dimethylhexanoate Chemical compound CCOC(=O)C(C)(C)CCCCBr CSQGAUJUODHNIM-UHFFFAOYSA-N 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• 230000000302 ischemic effect Effects 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 230000004898 mitochondrial function Effects 0.000 description 3
• QWLISCJHYITNQF-UHFFFAOYSA-N n-methoxy-1-phenylmethanamine Chemical compound CONCC1=CC=CC=C1 QWLISCJHYITNQF-UHFFFAOYSA-N 0.000 description 3
• LAWLETDOJIIYNQ-UHFFFAOYSA-N n-prop-2-ynyl-4-(trifluoromethoxy)benzamide Chemical compound FC(F)(F)OC1=CC=C(C(=O)NCC#C)C=C1 LAWLETDOJIIYNQ-UHFFFAOYSA-N 0.000 description 3
• 230000001338 necrotic effect Effects 0.000 description 3
• 238000001422 normality test Methods 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 238000000528 statistical test Methods 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• UTOIEVWJKDLJGE-AQRBRUGDSA-N (4r,6s)-6-[(e)-2-[4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyrimidin-5-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C=1C=C(F)C=CC=1C1=NC(C(C)C)=NC(C(C)C)=C1\C=C\[C@@H]1C[C@@H](O)CC(=O)O1 UTOIEVWJKDLJGE-AQRBRUGDSA-N 0.000 description 2
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 2
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 2
• GJWSUKYXUMVMGX-SECBINFHSA-N (R)-citronellic acid Chemical compound OC(=O)C[C@H](C)CCC=C(C)C GJWSUKYXUMVMGX-SECBINFHSA-N 0.000 description 2
• NEHNMFOYXAPHSD-JTQLQIEISA-N (S)-(-)-Citronellal Chemical compound O=CC[C@@H](C)CCC=C(C)C NEHNMFOYXAPHSD-JTQLQIEISA-N 0.000 description 2
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
• GJWSUKYXUMVMGX-VIFPVBQESA-N (S)-citronellic acid Chemical compound OC(=O)C[C@@H](C)CCC=C(C)C GJWSUKYXUMVMGX-VIFPVBQESA-N 0.000 description 2
• QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 2
• WAUNFWSVXRPCDQ-UHFFFAOYSA-N 1-(bromomethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CBr WAUNFWSVXRPCDQ-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• YJCNPPLLNNZSJA-UHFFFAOYSA-N 1-[(2-methoxyphenyl)methyl]-5-methyl-2-[4-(trifluoromethoxy)phenyl]imidazole Chemical compound COC1=C(CN2C(C)=CN=C2C2=CC=C(OC(F)(F)F)C=C2)C=CC=C1 YJCNPPLLNNZSJA-UHFFFAOYSA-N 0.000 description 2
• SWDKWZQLMUSLRH-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-1h-imidazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NC=CN1 SWDKWZQLMUSLRH-UHFFFAOYSA-N 0.000 description 2
• XYDNTALWFYHWQB-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-4,5-dihydro-1h-imidazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NCCN1 XYDNTALWFYHWQB-UHFFFAOYSA-N 0.000 description 2
• CUVCBLWSYZWJDZ-UHFFFAOYSA-N 2-[[5-methyl-2-[4-(trifluoromethoxy)phenyl]imidazol-1-yl]methyl]phenol Chemical compound CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)OC(F)(F)F CUVCBLWSYZWJDZ-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
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
• MTTGBJUPTVODIM-UHFFFAOYSA-N 4-(difluoromethoxy)-n-prop-2-ynylbenzamide Chemical compound FC(F)OC1=CC=C(C(=O)NCC#C)C=C1 MTTGBJUPTVODIM-UHFFFAOYSA-N 0.000 description 2
• HYGJKOLKSPIJLO-UHFFFAOYSA-N 4-chloro-3-fluoro-N-prop-2-ynylbenzamide Chemical compound ClC1=C(C=C(C(=O)NCC#C)C=C1)F HYGJKOLKSPIJLO-UHFFFAOYSA-N 0.000 description 2
• HVGGGWWCXFNXPI-UHFFFAOYSA-N 4-chloro-n-prop-2-ynylbenzamide Chemical compound ClC1=CC=C(C(=O)NCC#C)C=C1 HVGGGWWCXFNXPI-UHFFFAOYSA-N 0.000 description 2
• NXBDZSMRZFFVBA-UHFFFAOYSA-N 4-fluoro-n-prop-2-ynylbenzamide Chemical compound FC1=CC=C(C(=O)NCC#C)C=C1 NXBDZSMRZFFVBA-UHFFFAOYSA-N 0.000 description 2
• HHGZOEBSPZSATM-UHFFFAOYSA-N 4-methylsulfanyl-n-prop-2-ynylbenzamide Chemical compound CSC1=CC=C(C(=O)NCC#C)C=C1 HHGZOEBSPZSATM-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
• BVYFUUWYVRDPNQ-UHFFFAOYSA-N 5-(1h-imidazol-2-yl)-2-(trifluoromethyl)pyridine Chemical compound C1=NC(C(F)(F)F)=CC=C1C1=NC=CN1 BVYFUUWYVRDPNQ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 2
• 102100026189 Beta-galactosidase Human genes 0.000 description 2
• FEFPYRHSFYLOOH-UHFFFAOYSA-N BrC1=CN=C(N1CC1=C(C=CC=C1)OC)C1=CC=C(C=C1)C(F)(F)F Chemical compound BrC1=CN=C(N1CC1=C(C=CC=C1)OC)C1=CC=C(C=C1)C(F)(F)F FEFPYRHSFYLOOH-UHFFFAOYSA-N 0.000 description 2
• REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 2
• HACGKBBHYYAQQF-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(Br)C=CC=C1)C1=CC=C(C=C1)C(F)F Chemical compound CC1=CN=C(N1CC1=C(Br)C=CC=C1)C1=CC=C(C=C1)C(F)F HACGKBBHYYAQQF-UHFFFAOYSA-N 0.000 description 2
• ULPLVTSBISQVDW-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C Chemical compound CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C ULPLVTSBISQVDW-UHFFFAOYSA-N 0.000 description 2
• HMNAPLQUTZADTN-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)SC Chemical compound CC1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)SC HMNAPLQUTZADTN-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
• UOEKCBOENFGRLG-UHFFFAOYSA-N CC1=CN=C(N1CC1=C(Cl)C=CC=C1)C1=CC=C(OC(F)F)C=C1 Chemical compound CC1=CN=C(N1CC1=C(Cl)C=CC=C1)C1=CC=C(OC(F)F)C=C1 UOEKCBOENFGRLG-UHFFFAOYSA-N 0.000 description 2
• OOQYTUDCOJNPET-UHFFFAOYSA-N COC1=C(CN2C(=NC=C2)C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C(=NC=C2)C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 OOQYTUDCOJNPET-UHFFFAOYSA-N 0.000 description 2
• UKKFYSLMACHPAJ-FIBGUPNXSA-N COC1=C(CN2C(=NC=C2C([2H])([2H])[2H])C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C(=NC=C2C([2H])([2H])[2H])C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 UKKFYSLMACHPAJ-FIBGUPNXSA-N 0.000 description 2
• JDBKDVARMHDHEK-UHFFFAOYSA-N COC1=C(CN2C(C)=CN=C2C2=CC=C(C)C=C2)C=CC=C1 Chemical compound COC1=C(CN2C(C)=CN=C2C2=CC=C(C)C=C2)C=CC=C1 JDBKDVARMHDHEK-UHFFFAOYSA-N 0.000 description 2
• PHFHDUSAONDBHH-UHFFFAOYSA-N COC1=C(CN2C=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=CC=C1 PHFHDUSAONDBHH-UHFFFAOYSA-N 0.000 description 2
• SKVCAEHZKNWAQZ-UHFFFAOYSA-N CSC1=CC=C(C=C1)C1=NC=C(C)N1CC1=C(Br)C=CC=C1 Chemical compound CSC1=CC=C(C=C1)C1=NC=C(C)N1CC1=C(Br)C=CC=C1 SKVCAEHZKNWAQZ-UHFFFAOYSA-N 0.000 description 2
• IGEYBBZLLOTKIF-LJQANCHMSA-N C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C Chemical compound C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C IGEYBBZLLOTKIF-LJQANCHMSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• AAXVGCQJHPUCKW-UHFFFAOYSA-N ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC)F Chemical compound ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC)F AAXVGCQJHPUCKW-UHFFFAOYSA-N 0.000 description 2
• CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 2
• CWPAMLOOIUMUCY-UHFFFAOYSA-N ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O Chemical compound ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O CWPAMLOOIUMUCY-UHFFFAOYSA-N 0.000 description 2
• IERITXNGOQFRTP-UHFFFAOYSA-N ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC Chemical compound ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC IERITXNGOQFRTP-UHFFFAOYSA-N 0.000 description 2
• MUHAFFSXFYIHJM-QGZVFWFLSA-N ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 Chemical compound ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 MUHAFFSXFYIHJM-QGZVFWFLSA-N 0.000 description 2
• QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen 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
• 102000001039 Dystrophin Human genes 0.000 description 2
• 108010069091 Dystrophin Proteins 0.000 description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
• PDIANGAPEBVNHN-UHFFFAOYSA-N FC(C1=CC=C(C(=O)NCC#C)C=C1)F Chemical compound FC(C1=CC=C(C(=O)NCC#C)C=C1)F PDIANGAPEBVNHN-UHFFFAOYSA-N 0.000 description 2
• XJDLMVBBVWSTEO-UHFFFAOYSA-N FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O Chemical compound FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O XJDLMVBBVWSTEO-UHFFFAOYSA-N 0.000 description 2
• FIYZTKRBIJNZGH-UHFFFAOYSA-N FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC Chemical compound FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC FIYZTKRBIJNZGH-UHFFFAOYSA-N 0.000 description 2
• OAEPLYNAKJZLSC-QGZVFWFLSA-N FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 Chemical compound FC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 OAEPLYNAKJZLSC-QGZVFWFLSA-N 0.000 description 2
• ZRDBAAOJROODQL-UHFFFAOYSA-N FC=1C=C(C(=O)NCC#C)C=CC=1C(F)(F)F Chemical compound FC=1C=C(C(=O)NCC#C)C=CC=1C(F)(F)F ZRDBAAOJROODQL-UHFFFAOYSA-N 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 102100039556 Galectin-4 Human genes 0.000 description 2
• 241001559542 Hippocampus hippocampus Species 0.000 description 2
• 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
• 238000001282 Kruskal–Wallis one-way analysis of variance Methods 0.000 description 2
• 108060001084 Luciferase Proteins 0.000 description 2
• 239000005089 Luciferase Substances 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000872931 Myoporum sandwicense Species 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• QACOEHQFENZDIO-UHFFFAOYSA-N N1C(=NCC1)C=1C=CC(=NC=1)C(F)(F)F Chemical compound N1C(=NCC1)C=1C=CC(=NC=1)C(F)(F)F QACOEHQFENZDIO-UHFFFAOYSA-N 0.000 description 2
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 208000032109 Transient ischaemic attack Diseases 0.000 description 2
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 238000013019 agitation Methods 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 239000002585 base Substances 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 108010005774 beta-Galactosidase Proteins 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
• RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 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 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 239000002131 composite material Substances 0.000 description 2
• 229960003624 creatine Drugs 0.000 description 2
• 239000006046 creatine Substances 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 230000007547 defect Effects 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000000132 electrospray ionisation Methods 0.000 description 2
• 238000000921 elemental analysis Methods 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 2
• BUZPORNLCIEDRH-YHMJZVADSA-N ethyl (3R)-5-(3,3-dimethyloxiran-2-yl)-3-methylpentanoate Chemical compound CC1(C(O1)CC[C@H](CC(=O)OCC)C)C BUZPORNLCIEDRH-YHMJZVADSA-N 0.000 description 2
• SSJQOTXWMLWHOK-MRVPVSSYSA-N ethyl (3R)-6-hydroxy-3-methylhexanoate Chemical compound OCCC[C@H](CC(=O)OCC)C SSJQOTXWMLWHOK-MRVPVSSYSA-N 0.000 description 2
• UFPASQFPTYKYJI-VIFPVBQESA-N ethyl (3S)-3-methyl-6-methylsulfonyloxyhexanoate Chemical compound C[C@H](CC(=O)OCC)CCCOS(=O)(=O)C UFPASQFPTYKYJI-VIFPVBQESA-N 0.000 description 2
• BUZPORNLCIEDRH-RGURZIINSA-N ethyl (3S)-5-(3,3-dimethyloxiran-2-yl)-3-methylpentanoate Chemical compound CC1(C(O1)CC[C@@H](CC(=O)OCC)C)C BUZPORNLCIEDRH-RGURZIINSA-N 0.000 description 2
• SSJQOTXWMLWHOK-QMMMGPOBSA-N ethyl (3S)-6-hydroxy-3-methylhexanoate Chemical compound OCCC[C@@H](CC(=O)OCC)C SSJQOTXWMLWHOK-QMMMGPOBSA-N 0.000 description 2
• UAIOJGGMISJMMY-LLVKDONJSA-N ethyl (3r)-3,7-dimethyloct-6-enoate Chemical compound CCOC(=O)C[C@H](C)CCC=C(C)C UAIOJGGMISJMMY-LLVKDONJSA-N 0.000 description 2
• RTMVZAZNAONVCQ-MRVPVSSYSA-N ethyl (3r)-3-methyl-6-oxohexanoate Chemical compound CCOC(=O)C[C@H](C)CCC=O RTMVZAZNAONVCQ-MRVPVSSYSA-N 0.000 description 2
• UAIOJGGMISJMMY-NSHDSACASA-N ethyl (3s)-3,7-dimethyloct-6-enoate Chemical compound CCOC(=O)C[C@@H](C)CCC=C(C)C UAIOJGGMISJMMY-NSHDSACASA-N 0.000 description 2
• RTMVZAZNAONVCQ-QMMMGPOBSA-N ethyl (3s)-3-methyl-6-oxohexanoate Chemical compound CCOC(=O)C[C@@H](C)CCC=O RTMVZAZNAONVCQ-QMMMGPOBSA-N 0.000 description 2
• 230000003203 everyday effect Effects 0.000 description 2
• 230000004129 fatty acid metabolism Effects 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 238000010166 immunofluorescence Methods 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 229960002725 isoflurane Drugs 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 208000037806 kidney injury Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 230000004065 mitochondrial dysfunction Effects 0.000 description 2
• 230000002438 mitochondrial effect Effects 0.000 description 2
• 210000000663 muscle cell Anatomy 0.000 description 2
• 206010028320 muscle necrosis Diseases 0.000 description 2
• 210000003098 myoblast Anatomy 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
• 238000001543 one-way ANOVA Methods 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• 239000002504 physiological saline solution Substances 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• 239000013612 plasmid Substances 0.000 description 2
• 229920000728 polyester Polymers 0.000 description 2
• 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 2
• 238000010926 purge Methods 0.000 description 2
• 239000008213 purified water Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000010410 reperfusion Effects 0.000 description 2
• 230000029058 respiratory gaseous exchange Effects 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 239000012266 salt solution Substances 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 210000002363 skeletal muscle cell Anatomy 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 210000002435 tendon Anatomy 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 201000010875 transient cerebral ischemia Diseases 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• NZGWDASTMWDZIW-MRVPVSSYSA-N (+)-pulegone Chemical compound C[C@@H]1CCC(=C(C)C)C(=O)C1 NZGWDASTMWDZIW-MRVPVSSYSA-N 0.000 description 1
• MNULEGDCPYONBU-UIXCWHRQSA-N (1R,4E,5'S,6S,6'S,7R,8S,10R,11R,12S,14R,15S,16R,18Z,20Z,22R,25S,27R,28S,29R)-22-ethyl-7,11,14,15-tetrahydroxy-6'-[(2R)-2-hydroxypropyl]-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C/C=C\1)[C@@H]2C MNULEGDCPYONBU-UIXCWHRQSA-N 0.000 description 1
• MNULEGDCPYONBU-CBLVMMTCSA-N (1R,4Z,5'S,6S,6'S,7R,8S,10R,11R,12S,14R,15S,16R,18Z,20Z,22R,25S,27R,28S,29R)-22-ethyl-7,11,14,15-tetrahydroxy-6'-[(2R)-2-hydroxypropyl]-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C/[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C/C=C\1)[C@@H]2C MNULEGDCPYONBU-CBLVMMTCSA-N 0.000 description 1
• MNULEGDCPYONBU-WABYXMGOSA-N (1S,4E,5'R,6R,6'R,7S,8R,10S,11S,12R,14S,15R,16S,18E,22S,25R,27S,28R,29S)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC[C@H]1CC[C@H]2O[C@@]3(CC[C@@H](C)[C@@H](CC(C)O)O3)[C@H](C)[C@@H](OC(=O)\C=C\[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@](C)(O)[C@H](O)[C@@H](C)C\C=C\C=C1)[C@H]2C MNULEGDCPYONBU-WABYXMGOSA-N 0.000 description 1
• MNULEGDCPYONBU-QECWTJOCSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-QECWTJOCSA-N 0.000 description 1
• MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 1
• MNULEGDCPYONBU-BOXGPLBDSA-N (1r,4s,5e,5'r,6'r,7e,10s,11s,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-BOXGPLBDSA-N 0.000 description 1
• NOYASZMZIBFFNZ-UHFFFAOYSA-N (2-bromophenyl)methanamine Chemical compound NCC1=CC=CC=C1Br NOYASZMZIBFFNZ-UHFFFAOYSA-N 0.000 description 1
• KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 1
• XQXMDYVBIZPDHE-UHFFFAOYSA-N (2-methoxy-5-methylphenyl)methanamine Chemical compound COC1=CC=C(C)C=C1CN XQXMDYVBIZPDHE-UHFFFAOYSA-N 0.000 description 1
• RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
• FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 description 1
• VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
• MNULEGDCPYONBU-YOKYSHDFSA-N (5'R,10S,11R,12S,14S,15R,16R,18R,19S,20R,26R,29S)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2S)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C=CC(=O)OC([C@H]1C)[C@H]2C)C=CC=CC(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-YOKYSHDFSA-N 0.000 description 1
• IYQIJUZZRLPXIL-UHFFFAOYSA-N (5-fluoro-2-methoxyphenyl)methanamine Chemical compound COC1=CC=C(F)C=C1CN IYQIJUZZRLPXIL-UHFFFAOYSA-N 0.000 description 1
• MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• PHIQHXFUZVPYII-ZCFIWIBFSA-O (R)-carnitinium Chemical compound C[N+](C)(C)C[C@H](O)CC(O)=O PHIQHXFUZVPYII-ZCFIWIBFSA-O 0.000 description 1
• 235000012121 (S)-(-)-citronellal Nutrition 0.000 description 1
• BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-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
• LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-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
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• YTTWDTVYXAEAJA-UHFFFAOYSA-M 2,2-dimethylhexanoate Chemical compound CCCCC(C)(C)C([O-])=O YTTWDTVYXAEAJA-UHFFFAOYSA-M 0.000 description 1
• LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 description 1
• ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 description 1
• HRPKMEWDMLPBGU-UHFFFAOYSA-N 2-[[2-[4-(furan-2-yl)phenyl]-5-methylimidazol-1-yl]methyl]phenol Chemical compound O1C(=CC=C1)C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O HRPKMEWDMLPBGU-UHFFFAOYSA-N 0.000 description 1
• 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
• 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
• HRIHSNPFVGMAKX-UHFFFAOYSA-N 3-fluoro-4-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)C(F)=C1 HRIHSNPFVGMAKX-UHFFFAOYSA-N 0.000 description 1
• NZQMQVJXSRMTCJ-UHFFFAOYSA-M 3-methylhexanoate Chemical compound CCCC(C)CC([O-])=O NZQMQVJXSRMTCJ-UHFFFAOYSA-M 0.000 description 1
• BSNNYLYELGBSBA-UHFFFAOYSA-N 4-(difluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)F)C=C1 BSNNYLYELGBSBA-UHFFFAOYSA-N 0.000 description 1
• AVYXJQFZBUXNHB-UHFFFAOYSA-N 4-(difluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(C(F)F)C=C1 AVYXJQFZBUXNHB-UHFFFAOYSA-N 0.000 description 1
• RATSANVPHHXDCT-UHFFFAOYSA-N 4-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)(F)F)C=C1 RATSANVPHHXDCT-UHFFFAOYSA-N 0.000 description 1
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
• QPIBHIXKUQKNFP-UHFFFAOYSA-N 4-chloro-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C(F)=C1 QPIBHIXKUQKNFP-UHFFFAOYSA-N 0.000 description 1
• XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
• BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 1
• 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 1
• KWHCPERWLHBLOT-UHFFFAOYSA-N 4-methylsulfanylbenzoic acid Chemical compound CSC1=CC=C(C(O)=O)C=C1 KWHCPERWLHBLOT-UHFFFAOYSA-N 0.000 description 1
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
• MRPAGRCGPAXOGS-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carbaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=N1 MRPAGRCGPAXOGS-UHFFFAOYSA-N 0.000 description 1
• 230000002407 ATP formation Effects 0.000 description 1
• 208000010444 Acidosis Diseases 0.000 description 1
• 101710134784 Agnoprotein Proteins 0.000 description 1
• 239000012103 Alexa Fluor 488 Substances 0.000 description 1
• RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
• 229920000856 Amylose Polymers 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• UIFFUZWRFRDZJC-UHFFFAOYSA-N Antimycin A1 Natural products CC1OC(=O)C(CCCCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-UHFFFAOYSA-N 0.000 description 1
• NQWZLRAORXLWDN-UHFFFAOYSA-N Antimycin-A Natural products CCCCCCC(=O)OC1C(C)OC(=O)C(NC(=O)c2ccc(NC=O)cc2O)C(C)OC(=O)C1CCCC NQWZLRAORXLWDN-UHFFFAOYSA-N 0.000 description 1
• 201000006935 Becker muscular dystrophy Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• UXUZSRCJMPRAPX-UHFFFAOYSA-N BrC1=CN=C(N1CC1=C(C=CC=C1)OC)C=1C=CC(=NC=1)C(F)(F)F Chemical compound BrC1=CN=C(N1CC1=C(C=CC=C1)OC)C=1C=CC(=NC=1)C(F)(F)F UXUZSRCJMPRAPX-UHFFFAOYSA-N 0.000 description 1
• UETWPXKPFLUIMG-UHFFFAOYSA-N BrC=1N=C(N(C=1)CC1=C(C=CC=C1)OC)C=1C=CC(=NC=1)C(F)(F)F Chemical compound BrC=1N=C(N(C=1)CC1=C(C=CC=C1)OC)C=1C=CC(=NC=1)C(F)(F)F UETWPXKPFLUIMG-UHFFFAOYSA-N 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• QZWQLFCJTVVBIU-FIBGUPNXSA-N C(C1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C(F)(F)F)([2H])([2H])[2H] Chemical compound C(C1=CN=C(N1CC1=C(C=CC=C1)O)C1=CC=C(C=C1)C(F)(F)F)([2H])([2H])[2H] QZWQLFCJTVVBIU-FIBGUPNXSA-N 0.000 description 1
• OMCDNQOMTAHLDT-FIBGUPNXSA-N C(C1=CN=C(N1CC1=C(C=CC=C1)O)C=1C=NC(=CC=1)C(F)(F)F)([2H])([2H])[2H] Chemical compound C(C1=CN=C(N1CC1=C(C=CC=C1)O)C=1C=NC(=CC=1)C(F)(F)F)([2H])([2H])[2H] OMCDNQOMTAHLDT-FIBGUPNXSA-N 0.000 description 1
• NCAIVHUTUKZEIG-UHFFFAOYSA-N CC(C(=O)O)(CCCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F)C Chemical compound CC(C(=O)O)(CCCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F)C NCAIVHUTUKZEIG-UHFFFAOYSA-N 0.000 description 1
• PTMRJDTVDCAPQL-UHFFFAOYSA-N CC1=CC(=C(C=C1)O)CN1C(=NC=C1C)C1=CC=C(C=C1)OC(F)(F)F Chemical compound CC1=CC(=C(C=C1)O)CN1C(=NC=C1C)C1=CC=C(C=C1)OC(F)(F)F PTMRJDTVDCAPQL-UHFFFAOYSA-N 0.000 description 1
• MNULEGDCPYONBU-MQLHLVDXSA-N CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C\C=C\1)C2C Polymers CC[C@@H]1CC[C@@H]2O[C@]3(CC[C@H](C)[C@H](C[C@@H](C)O)O3)[C@@H](C)[C@H](OC(=O)\C=C\[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@](C)(O)[C@@H](O)[C@H](C)C\C=C\C=C\1)C2C MNULEGDCPYONBU-MQLHLVDXSA-N 0.000 description 1
• WNDPXYAVRBQZAL-FIBGUPNXSA-N COC1=C(CN2C(=NC=C2C([2H])([2H])[2H])C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 Chemical compound COC1=C(CN2C(=NC=C2C([2H])([2H])[2H])C=2C=CC(=NC=2)C(F)(F)F)C=CC=C1 WNDPXYAVRBQZAL-FIBGUPNXSA-N 0.000 description 1
• NRKHBJXGTNFZGX-UHFFFAOYSA-N COC1=C(CN2C(C)=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=C(F)C=C1 Chemical compound COC1=C(CN2C(C)=CN=C2C2=CC=C(C=C2)C(F)(F)F)C=C(F)C=C1 NRKHBJXGTNFZGX-UHFFFAOYSA-N 0.000 description 1
• LZUVKZDRTBNTLH-UHFFFAOYSA-N COC1=C(CN2C(C)=CN=C2C2=CC=C(OC(F)(F)F)C=C2)C=C(C)C=C1 Chemical compound COC1=C(CN2C(C)=CN=C2C2=CC=C(OC(F)(F)F)C=C2)C=C(C)C=C1 LZUVKZDRTBNTLH-UHFFFAOYSA-N 0.000 description 1
• FMOPHFSPINWSOV-QGZVFWFLSA-N C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F Chemical compound C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F FMOPHFSPINWSOV-QGZVFWFLSA-N 0.000 description 1
• GYNMVDMBFKGCCR-QGZVFWFLSA-N C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)OC(F)(F)F Chemical compound C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)OC(F)(F)F GYNMVDMBFKGCCR-QGZVFWFLSA-N 0.000 description 1
• PASBPZUWNUNJHE-GOSISDBHSA-N C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)SC Chemical compound C[C@@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)SC PASBPZUWNUNJHE-GOSISDBHSA-N 0.000 description 1
• FMOPHFSPINWSOV-KRWDZBQOSA-N C[C@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F Chemical compound C[C@H](CC(=O)O)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F FMOPHFSPINWSOV-KRWDZBQOSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• DVSOWTHUYYMROI-UHFFFAOYSA-N ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F Chemical compound ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F DVSOWTHUYYMROI-UHFFFAOYSA-N 0.000 description 1
• GCESMSWRWMRRHD-UHFFFAOYSA-N ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCCCC(C(=O)O)(C)C)C=CC=C1)F Chemical compound ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCCCC(C(=O)O)(C)C)C=CC=C1)F GCESMSWRWMRRHD-UHFFFAOYSA-N 0.000 description 1
• ZYSIAQDFLFFVJJ-MRXNPFEDSA-N ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F Chemical compound ClC1=C(C=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F ZYSIAQDFLFFVJJ-MRXNPFEDSA-N 0.000 description 1
• 206010009895 Colitis ischaemic Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 206010011703 Cyanosis Diseases 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 238000001061 Dunnett's test Methods 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• LJNHWBQXFHWTAE-UHFFFAOYSA-N FC(C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F Chemical compound FC(C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F LJNHWBQXFHWTAE-UHFFFAOYSA-N 0.000 description 1
• GZOBAVBBIIMOMF-QGZVFWFLSA-N FC(C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F Chemical compound FC(C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F GZOBAVBBIIMOMF-QGZVFWFLSA-N 0.000 description 1
• LRFSWJDKLIGMQF-UHFFFAOYSA-N FC(OC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F Chemical compound FC(OC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O)F LRFSWJDKLIGMQF-UHFFFAOYSA-N 0.000 description 1
• IMECUCANUVGFRR-QGZVFWFLSA-N FC(OC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F Chemical compound FC(OC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1)F IMECUCANUVGFRR-QGZVFWFLSA-N 0.000 description 1
• FCDMNOQYZJZVGW-UHFFFAOYSA-N FC1=CC(=C(C=C1)O)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F Chemical compound FC1=CC(=C(C=C1)O)CN1C(=NC=C1C)C1=CC=C(C=C1)C(F)(F)F FCDMNOQYZJZVGW-UHFFFAOYSA-N 0.000 description 1
• HDPLLLVBYLXKFZ-UHFFFAOYSA-N FC=1C=C(C=CC=1C(F)(F)F)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O Chemical compound FC=1C=C(C=CC=1C(F)(F)F)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)O HDPLLLVBYLXKFZ-UHFFFAOYSA-N 0.000 description 1
• LSAQKOLJZVZIGV-UHFFFAOYSA-N FC=1C=C(C=CC=1C(F)(F)F)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC Chemical compound FC=1C=C(C=CC=1C(F)(F)F)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC LSAQKOLJZVZIGV-UHFFFAOYSA-N 0.000 description 1
• 208000037149 Facioscapulohumeral dystrophy Diseases 0.000 description 1
• 208000011514 Familial renal glucosuria Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010017711 Gangrene Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
• 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
• 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000741797 Homo sapiens Peroxisome proliferator-activated receptor delta Proteins 0.000 description 1
• 101001123331 Homo sapiens Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Proteins 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010021024 Hypolipidaemia Diseases 0.000 description 1
• WNJDGYOPALQKML-UHFFFAOYSA-N IC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC Chemical compound IC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(C=CC=C1)OC WNJDGYOPALQKML-UHFFFAOYSA-N 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 108010057186 Insulin Glargine Proteins 0.000 description 1
• COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 1
• 206010022680 Intestinal ischaemia Diseases 0.000 description 1
• 208000032382 Ischaemic stroke Diseases 0.000 description 1
• 239000012839 Krebs-Henseleit buffer Substances 0.000 description 1
• 238000012313 Kruskal-Wallis test Methods 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 1
• 101100355629 Mus musculus Ran gene Proteins 0.000 description 1
• 206010048654 Muscle fibrosis Diseases 0.000 description 1
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
• 102000034570 NR1 subfamily Human genes 0.000 description 1
• 108020001305 NR1 subfamily Proteins 0.000 description 1
• 238000011887 Necropsy Methods 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• XOFBESNFVYMKTL-HXUWFJFHSA-N O1C(=CC=C1)C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 Chemical compound O1C(=CC=C1)C1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)O)C)C=CC=C1 XOFBESNFVYMKTL-HXUWFJFHSA-N 0.000 description 1
• 208000004286 Osteochondrodysplasias Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 102100028960 Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Human genes 0.000 description 1
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 101100372319 Rattus norvegicus Utrn gene Proteins 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 208000018675 Schwartz-Jampel syndrome Diseases 0.000 description 1
• 201000003222 Schwartz-Jampel syndrome 1 Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• 229940123464 Thiazolidinedione Drugs 0.000 description 1
• JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
• FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
• QCSAGIPMTZIRPT-FIBGUPNXSA-N [2H]C([2H])([2H])C1=CN=C(N1)C2=CN=C(C=C2)C(F)(F)F Chemical compound [2H]C([2H])([2H])C1=CN=C(N1)C2=CN=C(C=C2)C(F)(F)F QCSAGIPMTZIRPT-FIBGUPNXSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000007950 acidosis Effects 0.000 description 1
• 208000026545 acidosis disease Diseases 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 208000012998 acute renal failure Diseases 0.000 description 1
• 230000001270 agonistic effect Effects 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
• 239000000883 anti-obesity agent Substances 0.000 description 1
• 230000002785 anti-thrombosis Effects 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 239000003472 antidiabetic agent Substances 0.000 description 1
• 229940125708 antidiabetic agent Drugs 0.000 description 1
• UIFFUZWRFRDZJC-SBOOETFBSA-N antimycin A Chemical compound C[C@H]1OC(=O)[C@H](CCCCCC)[C@@H](OC(=O)CC(C)C)[C@H](C)OC(=O)[C@H]1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-SBOOETFBSA-N 0.000 description 1
• PVEVXUMVNWSNIG-UHFFFAOYSA-N antimycin A3 Natural products CC1OC(=O)C(CCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O PVEVXUMVNWSNIG-UHFFFAOYSA-N 0.000 description 1
• VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
• RCHHVVGSTHAVPF-ZPHPLDECSA-N apidra Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3N=CNC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CNC=N1 RCHHVVGSTHAVPF-ZPHPLDECSA-N 0.000 description 1
• 229940112930 apidra Drugs 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 229940114079 arachidonic acid Drugs 0.000 description 1
• 235000021342 arachidonic acid Nutrition 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
• 229960000516 bezafibrate Drugs 0.000 description 1
• 230000027455 binding Effects 0.000 description 1
• 230000008436 biogenesis Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical group 0.000 description 1
• 229960003362 carbutamide Drugs 0.000 description 1
• VDTNNGKXZGSZIP-UHFFFAOYSA-N carbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VDTNNGKXZGSZIP-UHFFFAOYSA-N 0.000 description 1
• 229960004203 carnitine Drugs 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 238000000633 chiral stationary phase gas chromatography Methods 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 201000006815 congenital muscular dystrophy Diseases 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 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
• 238000007256 debromination reaction Methods 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 229910003460 diamond Inorganic materials 0.000 description 1
• 239000010432 diamond Substances 0.000 description 1
• 125000006010 dichloroethoxy group Chemical group 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
• 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
• 125000005072 dihydrothiopyranyl group Chemical group S1C(CCC=C1)* 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 208000037765 diseases and disorders Diseases 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
• 201000003079 ectropion Diseases 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 201000002491 encephalomyelitis Diseases 0.000 description 1
• GHJJKMSOYVEQSE-OAQYLSRUSA-N ethyl (3R)-3-methyl-6-[2-[[5-methyl-2-(4-methylphenyl)imidazol-1-yl]methyl]phenoxy]hexanoate Chemical compound C[C@@H](CC(=O)OCC)CCCOC1=C(C=CC=C1)CN1C(=NC=C1C)C1=CC=C(C=C1)C GHJJKMSOYVEQSE-OAQYLSRUSA-N 0.000 description 1
• FUSUZUAOTBPQAB-LJQANCHMSA-N ethyl (3R)-6-[2-[[2-(4-chlorophenyl)-5-methylimidazol-1-yl]methyl]phenoxy]-3-methylhexanoate Chemical compound ClC1=CC=C(C=C1)C=1N(C(=CN=1)C)CC1=C(OCCC[C@H](CC(=O)OCC)C)C=CC=C1 FUSUZUAOTBPQAB-LJQANCHMSA-N 0.000 description 1
• GYDLKDMRVQUKRY-AATRIKPKSA-N ethyl (E)-6-bromo-2,2-dimethylhex-4-enoate Chemical compound BrC/C=C/CC(C(=O)OCC)(C)C GYDLKDMRVQUKRY-AATRIKPKSA-N 0.000 description 1
• LJDWRBCSOFXMTM-SOFGYWHQSA-N ethyl (E)-6-bromo-4-methylhex-4-enoate Chemical compound BrC/C=C(/CCC(=O)OCC)\C LJDWRBCSOFXMTM-SOFGYWHQSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 238000013213 extrapolation Methods 0.000 description 1
• 208000008570 facioscapulohumeral muscular dystrophy Diseases 0.000 description 1
• ZZCHHVUQYRMYLW-HKBQPEDESA-N farglitazar Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 ZZCHHVUQYRMYLW-HKBQPEDESA-N 0.000 description 1
• 229950003707 farglitazar Drugs 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 229960002297 fenofibrate Drugs 0.000 description 1
• YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
• 229960001419 fenoprofen Drugs 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000006005 fluoroethoxy group Chemical group 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960003627 gemfibrozil Drugs 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 229960004580 glibenclamide Drugs 0.000 description 1
• 229960000346 gliclazide Drugs 0.000 description 1
• 229960004346 glimepiride Drugs 0.000 description 1
• WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
• 229960001381 glipizide Drugs 0.000 description 1
• ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
• 229960003468 gliquidone Drugs 0.000 description 1
• 229960003236 glisoxepide Drugs 0.000 description 1
• ZKUDBRCEOBOWLF-UHFFFAOYSA-N glisoxepide Chemical compound O1C(C)=CC(C(=O)NCCC=2C=CC(=CC=2)S(=O)(=O)NC(=O)NN2CCCCCC2)=N1 ZKUDBRCEOBOWLF-UHFFFAOYSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• NIDHFQDUBOVBKZ-UHFFFAOYSA-N hex-4-enoic acid Chemical compound CC=CCCC(O)=O NIDHFQDUBOVBKZ-UHFFFAOYSA-N 0.000 description 1
• JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
• 238000010562 histological examination Methods 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 208000029498 hypoalphalipoproteinemia Diseases 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000007654 immersion Methods 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 238000003125 immunofluorescent labeling Methods 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 238000010832 independent-sample T-test Methods 0.000 description 1
• 229960000905 indomethacin Drugs 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 239000004026 insulin derivative Substances 0.000 description 1
• 108700039926 insulin glulisine Proteins 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000007918 intramuscular administration Methods 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
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 201000008222 ischemic colitis Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940060975 lantus Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 201000002818 limb ischemia Diseases 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 229960000299 mazindol Drugs 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 230000006371 metabolic abnormality Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
• PIJFWZZQZKZLQP-FNORWQNLSA-N methyl (e)-6-bromo-4-methylhex-4-enoate Chemical compound COC(=O)CC\C(C)=C\CBr PIJFWZZQZKZLQP-FNORWQNLSA-N 0.000 description 1
• KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
• 229950009116 mevastatin Drugs 0.000 description 1
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000004769 mitochondrial stress Effects 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 229950001135 muraglitazar Drugs 0.000 description 1
• 230000004220 muscle function Effects 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 208000031225 myocardial ischemia Diseases 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
• NNJQGOZSAVIBQV-UHFFFAOYSA-N n-bromo-1-phenylmethanamine Chemical compound BrNCC1=CC=CC=C1 NNJQGOZSAVIBQV-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
• 125000001624 naphthyl group Chemical group 0.000 description 1
• PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
• 229950001628 netoglitazone Drugs 0.000 description 1
• 208000008795 neuromyelitis optica Diseases 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• MNULEGDCPYONBU-UHFFFAOYSA-N oligomycin A Natural products CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 1
• MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 1
• 238000012015 optical character recognition Methods 0.000 description 1
• 238000003305 oral gavage Methods 0.000 description 1
• 230000008816 organ damage Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 230000036284 oxygen consumption Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 230000006611 pharmacological activation Effects 0.000 description 1
• 229960005222 phenazone Drugs 0.000 description 1
• 229960003562 phentermine Drugs 0.000 description 1
• 229960002036 phenytoin Drugs 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 238000000634 powder X-ray diffraction Methods 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 201000001514 prostate carcinoma Diseases 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011552 rat model Methods 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• 208000007278 renal glycosuria Diseases 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000004202 respiratory function Effects 0.000 description 1
• 230000024977 response to activity Effects 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 229940080817 rotenone Drugs 0.000 description 1
• JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 235000000891 standard diet Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000012353 t test Methods 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 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
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 231100000399 thyrotoxic Toxicity 0.000 description 1
• 230000001897 thyrotoxic effect Effects 0.000 description 1
• 229960002277 tolazamide Drugs 0.000 description 1
• OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
• 229960005371 tolbutamide Drugs 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• NIDHFQDUBOVBKZ-NSCUHMNNSA-N trans-hex-4-enoic acid Chemical compound C\C=C\CCC(O)=O NIDHFQDUBOVBKZ-NSCUHMNNSA-N 0.000 description 1
• 239000012096 transfection reagent Substances 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
• XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 210000000658 ulnar nerve Anatomy 0.000 description 1
• 125000005500 uronium group Chemical group 0.000 description 1
• 239000002966 varnish Substances 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1