JP5546463B2 - キノロン化合物を含む薬剤 - Google Patents
キノロン化合物を含む薬剤 Download PDFInfo
- Publication number
- JP5546463B2 JP5546463B2 JP2010541367A JP2010541367A JP5546463B2 JP 5546463 B2 JP5546463 B2 JP 5546463B2 JP 2010541367 A JP2010541367 A JP 2010541367A JP 2010541367 A JP2010541367 A JP 2010541367A JP 5546463 B2 JP5546463 B2 JP 5546463B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- disease
- syndrome
- lower alkyl
- quinolin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003814 drug Substances 0.000 title claims description 13
- 229940079593 drug Drugs 0.000 title claims description 12
- 150000007660 quinolones Chemical class 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 201000010099 disease Diseases 0.000 claims description 47
- -1 Pyrrolidinylcarbonyl Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 36
- 208000011580 syndromic disease Diseases 0.000 claims description 30
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000001225 therapeutic effect Effects 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 15
- 230000004770 neurodegeneration Effects 0.000 claims description 15
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 230000004898 mitochondrial function Effects 0.000 claims description 14
- 206010008027 Cerebellar atrophy Diseases 0.000 claims description 12
- 230000007812 deficiency Effects 0.000 claims description 12
- 230000000750 progressive effect Effects 0.000 claims description 12
- 206010003591 Ataxia Diseases 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 230000000069 prophylactic effect Effects 0.000 claims description 11
- 230000001771 impaired effect Effects 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 230000005856 abnormality Effects 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 230000007658 neurological function Effects 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 206010003694 Atrophy Diseases 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 230000037444 atrophy Effects 0.000 claims description 7
- 230000004064 dysfunction Effects 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000014644 Brain disease Diseases 0.000 claims description 6
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 6
- 206010008748 Chorea Diseases 0.000 claims description 6
- 206010011878 Deafness Diseases 0.000 claims description 6
- 208000032274 Encephalopathy Diseases 0.000 claims description 6
- 208000021642 Muscular disease Diseases 0.000 claims description 6
- 208000002033 Myoclonus Diseases 0.000 claims description 6
- 206010028629 Myoglobinuria Diseases 0.000 claims description 6
- 201000009623 Myopathy Diseases 0.000 claims description 6
- 240000007817 Olea europaea Species 0.000 claims description 6
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 6
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 208000012601 choreatic disease Diseases 0.000 claims description 6
- 230000001684 chronic effect Effects 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- 230000007850 degeneration Effects 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 230000010370 hearing loss Effects 0.000 claims description 6
- 231100000888 hearing loss Toxicity 0.000 claims description 6
- 208000016354 hearing loss disease Diseases 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 230000003211 malignant effect Effects 0.000 claims description 6
- 230000002438 mitochondrial effect Effects 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 208000035172 MERRF Diseases 0.000 claims description 5
- 206010042928 Syringomyelia Diseases 0.000 claims description 5
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 5
- 230000003412 degenerative effect Effects 0.000 claims description 5
- 230000002496 gastric effect Effects 0.000 claims description 5
- 230000003387 muscular Effects 0.000 claims description 5
- 230000003252 repetitive effect Effects 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 102100032533 ADP/ATP translocase 1 Human genes 0.000 claims description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 3
- 206010002027 Amyotrophy Diseases 0.000 claims description 3
- 208000009017 Athetosis Diseases 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 208000035183 Benign hereditary chorea Diseases 0.000 claims description 3
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 claims description 3
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 241001112695 Clostridiales Species 0.000 claims description 3
- 208000026372 Congenital cystic kidney disease Diseases 0.000 claims description 3
- 102000012437 Copper-Transporting ATPases Human genes 0.000 claims description 3
- 102100025287 Cytochrome b Human genes 0.000 claims description 3
- 108010075028 Cytochromes b Proteins 0.000 claims description 3
- 201000003863 Dandy-Walker Syndrome Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 3
- 208000016192 Demyelinating disease Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 208000002603 Dopa-responsive dystonia Diseases 0.000 claims description 3
- 208000014094 Dystonic disease Diseases 0.000 claims description 3
- 102000015782 Electron Transport Complex III Human genes 0.000 claims description 3
- 108010024882 Electron Transport Complex III Proteins 0.000 claims description 3
- 206010059284 Epidermal necrosis Diseases 0.000 claims description 3
- 101000768061 Escherichia phage P1 Antirepressor protein 1 Proteins 0.000 claims description 3
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 3
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 3
- 206010064571 Gene mutation Diseases 0.000 claims description 3
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010019663 Hepatic failure Diseases 0.000 claims description 3
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 3
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 3
- 101000796932 Homo sapiens ADP/ATP translocase 1 Proteins 0.000 claims description 3
- 101000804964 Homo sapiens DNA polymerase subunit gamma-1 Proteins 0.000 claims description 3
- 101000595929 Homo sapiens POLG alternative reading frame Proteins 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 206010061598 Immunodeficiency Diseases 0.000 claims description 3
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 3
- 201000003533 Leber congenital amaurosis Diseases 0.000 claims description 3
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 3
- 208000035177 MELAS Diseases 0.000 claims description 3
- 208000002569 Machado-Joseph Disease Diseases 0.000 claims description 3
- 208000019695 Migraine disease Diseases 0.000 claims description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
- 108020005196 Mitochondrial DNA Proteins 0.000 claims description 3
- 208000014844 Mitochondrial neurogastrointestinal encephalomyopathy Diseases 0.000 claims description 3
- 206010031264 Osteonecrosis Diseases 0.000 claims description 3
- 102100035196 POLG alternative reading frame Human genes 0.000 claims description 3
- 206010056332 Panencephalitis Diseases 0.000 claims description 3
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 3
- 206010034010 Parkinsonism Diseases 0.000 claims description 3
- 206010065657 Paroxysmal choreoathetosis Diseases 0.000 claims description 3
- 208000013234 Pearson syndrome Diseases 0.000 claims description 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 3
- 206010036105 Polyneuropathy Diseases 0.000 claims description 3
- 201000009916 Postpartum depression Diseases 0.000 claims description 3
- 208000024777 Prion disease Diseases 0.000 claims description 3
- 208000033063 Progressive myoclonic epilepsy Diseases 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 206010037764 Radiation myelopathy Diseases 0.000 claims description 3
- 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 206010038422 Renal cortical necrosis Diseases 0.000 claims description 3
- 208000033626 Renal failure acute Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 208000006289 Rett Syndrome Diseases 0.000 claims description 3
- 208000034189 Sclerosis Diseases 0.000 claims description 3
- 208000027919 Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome Diseases 0.000 claims description 3
- 201000010001 Silicosis Diseases 0.000 claims description 3
- 201000010829 Spina bifida Diseases 0.000 claims description 3
- 208000006097 Spinal Dysraphism Diseases 0.000 claims description 3
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 3
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 claims description 3
- 206010072148 Stiff-Person syndrome Diseases 0.000 claims description 3
- 206010043189 Telangiectasia Diseases 0.000 claims description 3
- 206010044074 Torticollis Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 claims description 3
- 208000018839 Wilson disease Diseases 0.000 claims description 3
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 3
- 201000011040 acute kidney failure Diseases 0.000 claims description 3
- 208000012998 acute renal failure Diseases 0.000 claims description 3
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 3
- 229940126575 aminoglycoside Drugs 0.000 claims description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 208000007502 anemia Diseases 0.000 claims description 3
- 208000010123 anthracosis Diseases 0.000 claims description 3
- 208000025748 atypical depressive disease Diseases 0.000 claims description 3
- 210000004227 basal ganglia Anatomy 0.000 claims description 3
- 201000009267 bronchiectasis Diseases 0.000 claims description 3
- 210000003591 cerebellar nuclei Anatomy 0.000 claims description 3
- 206010008129 cerebral palsy Diseases 0.000 claims description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 230000001054 cortical effect Effects 0.000 claims description 3
- 230000003210 demyelinating effect Effects 0.000 claims description 3
- 208000024732 dysthymic disease Diseases 0.000 claims description 3
- 208000010118 dystonia Diseases 0.000 claims description 3
- 201000006517 essential tremor Diseases 0.000 claims description 3
- 208000007386 hepatic encephalopathy Diseases 0.000 claims description 3
- 201000003636 hereditary ataxia Diseases 0.000 claims description 3
- 208000008675 hereditary spastic paraplegia Diseases 0.000 claims description 3
- 230000007813 immunodeficiency Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 208000018197 inherited torticollis Diseases 0.000 claims description 3
- 208000005430 kidney cortex necrosis Diseases 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 208000007903 liver failure Diseases 0.000 claims description 3
- 231100000835 liver failure Toxicity 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 208000024714 major depressive disease Diseases 0.000 claims description 3
- 230000036244 malformation Effects 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 201000006938 muscular dystrophy Diseases 0.000 claims description 3
- 208000031225 myocardial ischemia Diseases 0.000 claims description 3
- 201000002648 nephronophthisis Diseases 0.000 claims description 3
- 201000009925 nephrosclerosis Diseases 0.000 claims description 3
- 201000001119 neuropathy Diseases 0.000 claims description 3
- 230000007823 neuropathy Effects 0.000 claims description 3
- 206010030875 ophthalmoplegia Diseases 0.000 claims description 3
- 208000013667 paroxysmal dyskinesia Diseases 0.000 claims description 3
- 230000000737 periodic effect Effects 0.000 claims description 3
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 3
- 208000000813 polyradiculoneuropathy Diseases 0.000 claims description 3
- 230000003449 preventive effect Effects 0.000 claims description 3
- 201000002241 progressive bulbar palsy Diseases 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 208000002916 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Diseases 0.000 claims description 3
- 230000001568 sexual effect Effects 0.000 claims description 3
- 230000001148 spastic effect Effects 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 208000009056 telangiectasis Diseases 0.000 claims description 3
- 231100000331 toxic Toxicity 0.000 claims description 3
- 230000002588 toxic effect Effects 0.000 claims description 3
- 206010006542 Bulbar palsy Diseases 0.000 claims description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
- 208000034800 Leukoencephalopathies Diseases 0.000 claims description 2
- 206010028851 Necrosis Diseases 0.000 claims description 2
- 208000035467 Pancreatic insufficiency Diseases 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 230000003376 axonal effect Effects 0.000 claims description 2
- 125000003725 azepanyl group Chemical group 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
- 230000002950 deficient Effects 0.000 claims description 2
- 230000006735 deficit Effects 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 230000017074 necrotic cell death Effects 0.000 claims description 2
- 208000001749 optic atrophy Diseases 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 208000012672 seasonal affective disease Diseases 0.000 claims description 2
- 208000009174 transverse myelitis Diseases 0.000 claims description 2
- 239000000843 powder Substances 0.000 description 113
- 150000001875 compounds Chemical class 0.000 description 62
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 229960003638 dopamine Drugs 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 8
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000007514 bases Chemical class 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- 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 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 102100033928 Sodium-dependent dopamine transporter Human genes 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 4
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- 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 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 229930195712 glutamate Natural products 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 0 *c(c(*)c1*)c(*)c2c1NC(*)=C(*)C2=O Chemical compound *c(c(*)c1*)c(*)c2c1NC(*)=C(*)C2=O 0.000 description 3
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 3
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 3
- 206010029260 Neuroblastoma Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000812 cholinergic antagonist Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000002532 enzyme inhibitor Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000001259 mesencephalon Anatomy 0.000 description 3
- 230000004065 mitochondrial dysfunction Effects 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000012264 purified product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 2
- AAAKPZCUPZUSIJ-UHFFFAOYSA-N 3-(2-chloro-6-fluorophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=C(F)C=CC=C1Cl AAAKPZCUPZUSIJ-UHFFFAOYSA-N 0.000 description 2
- NKQCAAADZHATII-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5,7-dimethyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=C(C)C=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 NKQCAAADZHATII-UHFFFAOYSA-N 0.000 description 2
- VDBGGUUJSBAFME-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-[methyl(propyl)amino]-1h-quinolin-4-one Chemical compound CCCN(C)C1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 VDBGGUUJSBAFME-UHFFFAOYSA-N 0.000 description 2
- FSECEUCVOZKSQX-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 FSECEUCVOZKSQX-UHFFFAOYSA-N 0.000 description 2
- PKZKAJZURUCKCJ-UHFFFAOYSA-N 4-methyl-2-nitro-1-propoxybenzene Chemical compound CCCOC1=CC=C(C)C=C1[N+]([O-])=O PKZKAJZURUCKCJ-UHFFFAOYSA-N 0.000 description 2
- BWRYWFOSRHSJGI-UHFFFAOYSA-N 5-methyl-2-propoxyaniline Chemical compound CCCOC1=CC=C(C)C=C1N BWRYWFOSRHSJGI-UHFFFAOYSA-N 0.000 description 2
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 2
- BAVQGGVWQKFELU-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-5-methoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=C(OC)C=C2)=O)=CNC1=C2OCC1CC1 BAVQGGVWQKFELU-UHFFFAOYSA-N 0.000 description 2
- NRGPBKQFSATARC-UHFFFAOYSA-N 8-[cyclohexyl(methyl)amino]-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N(C)C3CCCCC3)C=CC(C)=C2C1=O NRGPBKQFSATARC-UHFFFAOYSA-N 0.000 description 2
- OYXGVNKJJGIHJC-UHFFFAOYSA-N 8-imidazol-1-yl-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N3C=NC=C3)C=CC(C)=C2C1=O OYXGVNKJJGIHJC-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 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 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101001018717 Homo sapiens Mitofusin-2 Proteins 0.000 description 2
- 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 2
- 229920001543 Laminarin Polymers 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102100033703 Mitofusin-2 Human genes 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 239000005456 alcohol based solvent Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 210000005064 dopaminergic neuron Anatomy 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 239000004210 ether based solvent Substances 0.000 description 2
- SOJDEQBDCUGGEC-UHFFFAOYSA-N ethyl 3-hydroxy-2-(4-methoxyphenyl)prop-2-enoate Chemical compound CCOC(=O)C(=CO)C1=CC=C(OC)C=C1 SOJDEQBDCUGGEC-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- DBTMGCOVALSLOR-VPNXCSTESA-N laminarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](O)C(O[C@H]2[C@@H]([C@@H](CO)OC(O)[C@@H]2O)O)O[C@H](CO)[C@H]1O DBTMGCOVALSLOR-VPNXCSTESA-N 0.000 description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- 238000003354 tissue distribution assay Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- JIRHAGAOHOYLNO-UHFFFAOYSA-N (3-cyclopentyloxy-4-methoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C=C1OC1CCCC1 JIRHAGAOHOYLNO-UHFFFAOYSA-N 0.000 description 1
- DPEYHNFHDIXMNV-UHFFFAOYSA-N (9-amino-3-bicyclo[3.3.1]nonanyl)-(4-benzyl-5-methyl-1,4-diazepan-1-yl)methanone dihydrochloride Chemical compound Cl.Cl.CC1CCN(CCN1Cc1ccccc1)C(=O)C1CC2CCCC(C1)C2N DPEYHNFHDIXMNV-UHFFFAOYSA-N 0.000 description 1
- PCTZLSCYMRXUGW-UHFFFAOYSA-N 1,1,1,2,2-pentafluorobutane Chemical group [CH2]CC(F)(F)C(F)(F)F PCTZLSCYMRXUGW-UHFFFAOYSA-N 0.000 description 1
- FKTXDTWDCPTPHK-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical group FC(F)(F)[C](F)C(F)(F)F FKTXDTWDCPTPHK-UHFFFAOYSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- YFBUOPGRGXDPKN-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-(4-methoxyphenyl)-5-methyl-8-propoxyquinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C(C(C=2C=CC(OC)=CC=2)=C2)=O)=C1N2CC1CC1 YFBUOPGRGXDPKN-UHFFFAOYSA-N 0.000 description 1
- RBXGBVONDCFYLN-UHFFFAOYSA-N 1-ethyl-7-hydroxy-3-(4-methoxyphenyl)quinolin-4-one Chemical compound O=C1C2=CC=C(O)C=C2N(CC)C=C1C1=CC=C(OC)C=C1 RBXGBVONDCFYLN-UHFFFAOYSA-N 0.000 description 1
- YKTJSWNBTVFRFX-UHFFFAOYSA-N 1-ethyl-7-methoxy-3-(4-methoxyphenyl)quinolin-4-one Chemical compound O=C1C2=CC=C(OC)C=C2N(CC)C=C1C1=CC=C(OC)C=C1 YKTJSWNBTVFRFX-UHFFFAOYSA-N 0.000 description 1
- LELZNYWVNGROSL-UHFFFAOYSA-N 1-ethyl-7-methoxy-3-(4-phenylphenyl)quinolin-4-one Chemical compound O=C1C2=CC=C(OC)C=C2N(CC)C=C1C(C=C1)=CC=C1C1=CC=CC=C1 LELZNYWVNGROSL-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N 1H-quinolin-4-one Natural products C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- SYDNSSSQVSOXTN-UHFFFAOYSA-N 2-nitro-p-cresol Chemical compound CC1=CC=C(O)C([N+]([O-])=O)=C1 SYDNSSSQVSOXTN-UHFFFAOYSA-N 0.000 description 1
- AGBXYHCHUYARJY-UHFFFAOYSA-N 2-phenylethenesulfonic acid Chemical compound OS(=O)(=O)C=CC1=CC=CC=C1 AGBXYHCHUYARJY-UHFFFAOYSA-N 0.000 description 1
- GZTWFUADOHTMPZ-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound C1=C2OCOC2=CC(C2=CNC3=C(C2=O)C(C)=CC=C3OCCC)=C1 GZTWFUADOHTMPZ-UHFFFAOYSA-N 0.000 description 1
- BRVVIWFOMKLVPZ-UHFFFAOYSA-N 3-(1-benzothiophen-3-yl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound C1=CC=C2C(C3=CNC4=C(C3=O)C(C)=CC=C4OCCC)=CSC2=C1 BRVVIWFOMKLVPZ-UHFFFAOYSA-N 0.000 description 1
- RBLFVVSTFZRGPN-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)-5-methoxy-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=CC(OC)=C1OC RBLFVVSTFZRGPN-UHFFFAOYSA-N 0.000 description 1
- FODBBGXIIHOYKX-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=CC(OC)=C1OC FODBBGXIIHOYKX-UHFFFAOYSA-N 0.000 description 1
- LXHROJHWCZCEHM-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=CC(OC)=C1OC LXHROJHWCZCEHM-UHFFFAOYSA-N 0.000 description 1
- LBALBUWMXXWDKV-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-5-methoxy-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=C(Cl)C=C1Cl LBALBUWMXXWDKV-UHFFFAOYSA-N 0.000 description 1
- RZRIBSADVJOROE-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(Cl)C=C1Cl RZRIBSADVJOROE-UHFFFAOYSA-N 0.000 description 1
- JUAHTRVSIAMQDZ-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(Cl)C=C1Cl JUAHTRVSIAMQDZ-UHFFFAOYSA-N 0.000 description 1
- YSPSFYPRSUCJHV-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-5-methoxy-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1OC YSPSFYPRSUCJHV-UHFFFAOYSA-N 0.000 description 1
- CWKXVHZTGBQZJL-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1OC CWKXVHZTGBQZJL-UHFFFAOYSA-N 0.000 description 1
- OWIXLKOWXSTCPO-UHFFFAOYSA-N 3-(2,4-dimethoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1OC OWIXLKOWXSTCPO-UHFFFAOYSA-N 0.000 description 1
- MQYQOUJTMICBLA-UHFFFAOYSA-N 3-(2,5-dimethoxyphenyl)-5-methoxy-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC(OC)=CC=C1OC MQYQOUJTMICBLA-UHFFFAOYSA-N 0.000 description 1
- GIGPCMTWVHMEPT-UHFFFAOYSA-N 3-(2,5-dimethoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC(OC)=CC=C1OC GIGPCMTWVHMEPT-UHFFFAOYSA-N 0.000 description 1
- GIVPEKBGDRTPFS-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=C(Cl)C=CC=C1Cl GIVPEKBGDRTPFS-UHFFFAOYSA-N 0.000 description 1
- KPZKRIQMOXRCPQ-UHFFFAOYSA-N 3-(2-bromophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=CC=C1Br KPZKRIQMOXRCPQ-UHFFFAOYSA-N 0.000 description 1
- BZWILZMCFHBRAW-UHFFFAOYSA-N 3-(2-chloro-4-fluorophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(F)C=C1Cl BZWILZMCFHBRAW-UHFFFAOYSA-N 0.000 description 1
- OLDFVEBWHPPNLD-UHFFFAOYSA-N 3-(2-ethoxy-4-methoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1OCC OLDFVEBWHPPNLD-UHFFFAOYSA-N 0.000 description 1
- RVFYACUUXPYABQ-UHFFFAOYSA-N 3-(2-methoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=CC=C1OC RVFYACUUXPYABQ-UHFFFAOYSA-N 0.000 description 1
- ZBQXJFJKVTZCPO-UHFFFAOYSA-N 3-(2-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=CC=C1OC ZBQXJFJKVTZCPO-UHFFFAOYSA-N 0.000 description 1
- MLNAZKYTDFTMMH-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C(OC)=C1 MLNAZKYTDFTMMH-UHFFFAOYSA-N 0.000 description 1
- FDOZMEKALMXDKZ-UHFFFAOYSA-N 3-(3-bromophenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=CC(Br)=C1 FDOZMEKALMXDKZ-UHFFFAOYSA-N 0.000 description 1
- PADZPGFTTPXHRS-UHFFFAOYSA-N 3-(4-bromophenyl)-1-ethyl-7-methoxyquinolin-4-one Chemical compound O=C1C2=CC=C(OC)C=C2N(CC)C=C1C1=CC=C(Br)C=C1 PADZPGFTTPXHRS-UHFFFAOYSA-N 0.000 description 1
- UROUZJXPAOBYEO-UHFFFAOYSA-N 3-(4-bromophenyl)-8-propyl-1h-quinolin-4-one Chemical compound CCCC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(Br)C=C1 UROUZJXPAOBYEO-UHFFFAOYSA-N 0.000 description 1
- VTMDPZNVXMZTNN-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(O)C=C1 VTMDPZNVXMZTNN-UHFFFAOYSA-N 0.000 description 1
- PUIJKYZMTNWOLB-UHFFFAOYSA-N 3-(4-methoxy-2-methylphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1C PUIJKYZMTNWOLB-UHFFFAOYSA-N 0.000 description 1
- DYDLHFSDURVCEI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-(4-methylpiperazin-1-yl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N3CCN(C)CC3)C=CC(C)=C2C1=O DYDLHFSDURVCEI-UHFFFAOYSA-N 0.000 description 1
- HIVQFELPNUESDO-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-(pyrrolidine-1-carbonyl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C(=O)N3CCCC3)C=CC(C)=C2C1=O HIVQFELPNUESDO-UHFFFAOYSA-N 0.000 description 1
- VFRIMAVZZJQFDY-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-[methyl(2-methylpropyl)amino]-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N(C)CC(C)C)C=CC(C)=C2C1=O VFRIMAVZZJQFDY-UHFFFAOYSA-N 0.000 description 1
- CTTWKQUNQNNSKP-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-[methyl(propan-2-yl)amino]-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N(C)C(C)C)C=CC(C)=C2C1=O CTTWKQUNQNNSKP-UHFFFAOYSA-N 0.000 description 1
- XNVYVGYQTCEIGB-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-morpholin-4-yl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N3CCOCC3)C=CC(C)=C2C1=O XNVYVGYQTCEIGB-UHFFFAOYSA-N 0.000 description 1
- UEPRZQTYINVJTP-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-propylsulfanyl-1h-quinolin-4-one Chemical compound CCCSC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 UEPRZQTYINVJTP-UHFFFAOYSA-N 0.000 description 1
- MPIDMTSIOXLEGT-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-pyrrolidin-1-yl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N3CCCC3)C=CC(C)=C2C1=O MPIDMTSIOXLEGT-UHFFFAOYSA-N 0.000 description 1
- KYBSGBSBQAWPNC-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-thiophen-2-yl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C=3SC=CC=3)C=CC(C)=C2C1=O KYBSGBSBQAWPNC-UHFFFAOYSA-N 0.000 description 1
- NNOGZUGGRATXDD-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-methyl-8-thiophen-3-yl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C3=CSC=C3)C=CC(C)=C2C1=O NNOGZUGGRATXDD-UHFFFAOYSA-N 0.000 description 1
- ORWSOQALWWAQDW-UHFFFAOYSA-N 3-(4-methoxyphenyl)-5-phenyl-8-propoxy-1h-quinolin-4-one Chemical compound N1C=C(C=2C=CC(OC)=CC=2)C(=O)C2=C1C(OCCC)=CC=C2C1=CC=CC=C1 ORWSOQALWWAQDW-UHFFFAOYSA-N 0.000 description 1
- FUDZUHUSOLAPAI-UHFFFAOYSA-N 3-(4-methoxyphenyl)-6-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC(C)=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 FUDZUHUSOLAPAI-UHFFFAOYSA-N 0.000 description 1
- GIFODZGFFCEQAW-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-methyl-5-propoxy-1h-quinolin-4-one Chemical compound O=C1C=2C(OCCC)=CC=C(C)C=2NC=C1C1=CC=C(OC)C=C1 GIFODZGFFCEQAW-UHFFFAOYSA-N 0.000 description 1
- AFQLTJWGMGMLAE-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-phenoxy-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=CC=C2)=O)=CNC1=C2OC1=CC=CC=C1 AFQLTJWGMGMLAE-UHFFFAOYSA-N 0.000 description 1
- FZTKKQKMZQDSTN-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 FZTKKQKMZQDSTN-UHFFFAOYSA-N 0.000 description 1
- IAUIXKAKGUUXHR-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-propoxy-5-(trifluoromethyl)-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C(F)(F)F)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 IAUIXKAKGUUXHR-UHFFFAOYSA-N 0.000 description 1
- BRONKUPYXUKFAH-UHFFFAOYSA-N 3-(4-methoxyphenyl)-8-propyl-1h-quinolin-4-one Chemical compound CCCC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 BRONKUPYXUKFAH-UHFFFAOYSA-N 0.000 description 1
- DMKJZUOBSCCZJH-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n,n,5-trimethyl-4-oxo-1h-quinoline-8-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C(=O)N(C)C)C=CC(C)=C2C1=O DMKJZUOBSCCZJH-UHFFFAOYSA-N 0.000 description 1
- RDVPQUFNVHKJJA-UHFFFAOYSA-N 3-(4-methoxyphenyl)-n,n-dimethyl-4-oxo-8-propoxy-1h-quinoline-5-carboxamide Chemical compound CCCOC1=CC=C(C(=O)N(C)C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 RDVPQUFNVHKJJA-UHFFFAOYSA-N 0.000 description 1
- KCJXHGZJRHCXDI-UHFFFAOYSA-N 3-[3-(2,4-dimethoxyphenyl)phenyl]-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C(C=1)=CC=CC=1C1=CC=C(OC)C=C1OC KCJXHGZJRHCXDI-UHFFFAOYSA-N 0.000 description 1
- AKBJXGCGFNBGJF-UHFFFAOYSA-N 3-[3-(4-methylphenyl)phenyl]-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C(C=1)=CC=CC=1C1=CC=C(C)C=C1 AKBJXGCGFNBGJF-UHFFFAOYSA-N 0.000 description 1
- YUSWDCVQRXAIFD-UHFFFAOYSA-N 3-[4-(4-methoxyphenyl)phenyl]-8-propyl-1h-quinolin-4-one Chemical compound CCCC1=CC=CC(C2=O)=C1NC=C2C(C=C1)=CC=C1C1=CC=C(OC)C=C1 YUSWDCVQRXAIFD-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- JADKYXPJGLRATN-UHFFFAOYSA-N 3-naphthalen-1-yl-8-propoxy-1h-quinolin-4-one Chemical compound C1=CC=C2C(C3=CNC4=C(C3=O)C=CC=C4OCCC)=CC=CC2=C1 JADKYXPJGLRATN-UHFFFAOYSA-N 0.000 description 1
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical class C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 description 1
- 150000004331 4-hydroxyquinolines Chemical class 0.000 description 1
- GZWVHTKTSUYKBF-UHFFFAOYSA-N 5,6,7-trimethoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=CC(OC)=C(OC)C(OC)=C2C1=O GZWVHTKTSUYKBF-UHFFFAOYSA-N 0.000 description 1
- SPEUUXSDSNRWEX-UHFFFAOYSA-N 5,8-diethoxy-3-(4-fluorophenyl)-1h-quinolin-4-one Chemical compound CCOC1=CC=C(OCC)C(C2=O)=C1NC=C2C1=CC=C(F)C=C1 SPEUUXSDSNRWEX-UHFFFAOYSA-N 0.000 description 1
- HNQKDVZEXJIKEE-UHFFFAOYSA-N 5,8-diethoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound CCOC1=CC=C(OCC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 HNQKDVZEXJIKEE-UHFFFAOYSA-N 0.000 description 1
- SVGIDUUTBLBTPI-UHFFFAOYSA-N 5,8-dimethoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(OC)C=CC(OC)=C2C1=O SVGIDUUTBLBTPI-UHFFFAOYSA-N 0.000 description 1
- FYIICRUPRPDLRJ-UHFFFAOYSA-N 5-(methoxymethyl)-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(COC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 FYIICRUPRPDLRJ-UHFFFAOYSA-N 0.000 description 1
- SOUFKPWGMUZVQT-UHFFFAOYSA-N 5-cyclopropyl-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound N1C=C(C=2C=CC(OC)=CC=2)C(=O)C2=C1C(OCCC)=CC=C2C1CC1 SOUFKPWGMUZVQT-UHFFFAOYSA-N 0.000 description 1
- KJAQXSYTILOFCM-UHFFFAOYSA-N 5-ethyl-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(CC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 KJAQXSYTILOFCM-UHFFFAOYSA-N 0.000 description 1
- VQAGXVFTPDHMJH-UHFFFAOYSA-N 5-methoxy-3-(2-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=CC=C1OC VQAGXVFTPDHMJH-UHFFFAOYSA-N 0.000 description 1
- VYXUXLGWTLYHBA-UHFFFAOYSA-N 5-methoxy-3-(4-methoxyphenyl)-8-(2-methylpropoxy)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(OCC(C)C)C=CC(OC)=C2C1=O VYXUXLGWTLYHBA-UHFFFAOYSA-N 0.000 description 1
- TZENCPYRUGXHCL-UHFFFAOYSA-N 5-methoxy-3-(4-methoxyphenyl)-8-propan-2-yloxy-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(OC(C)C)C=CC(OC)=C2C1=O TZENCPYRUGXHCL-UHFFFAOYSA-N 0.000 description 1
- BVPRFXRJLJCKBH-UHFFFAOYSA-N 5-methoxy-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 BVPRFXRJLJCKBH-UHFFFAOYSA-N 0.000 description 1
- LJUAIQOCMIJHMC-UHFFFAOYSA-N 5-methoxy-3-naphthalen-1-yl-8-propoxy-1h-quinolin-4-one Chemical compound C1=CC=C2C(C3=CNC4=C(C3=O)C(OC)=CC=C4OCCC)=CC=CC2=C1 LJUAIQOCMIJHMC-UHFFFAOYSA-N 0.000 description 1
- PIWNSTRMUUWPRN-UHFFFAOYSA-N 5-methyl-3-(1-methylindol-3-yl)-8-propoxy-1h-quinolin-4-one Chemical compound C1=CC=C2C(C3=CNC4=C(C3=O)C(C)=CC=C4OCCC)=CN(C)C2=C1 PIWNSTRMUUWPRN-UHFFFAOYSA-N 0.000 description 1
- VIXLSCALETWXMH-UHFFFAOYSA-N 5-methyl-3-(2-methylphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=CC=C1C VIXLSCALETWXMH-UHFFFAOYSA-N 0.000 description 1
- CFIFAYKKDRTJGR-UHFFFAOYSA-N 5-methyl-3-(3-methyl-1-benzothiophen-2-yl)-8-propoxy-1h-quinolin-4-one Chemical compound S1C2=CC=CC=C2C(C)=C1C(C1=O)=CNC2=C1C(C)=CC=C2OCCC CFIFAYKKDRTJGR-UHFFFAOYSA-N 0.000 description 1
- NDCLCHPPEPMWCD-UHFFFAOYSA-N 5-methyl-8-propoxy-3-pyridin-4-yl-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=NC=C1 NDCLCHPPEPMWCD-UHFFFAOYSA-N 0.000 description 1
- WUCOIWUGQMIBIY-UHFFFAOYSA-N 5-methyl-8-propoxy-3-thiophen-2-yl-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=CS1 WUCOIWUGQMIBIY-UHFFFAOYSA-N 0.000 description 1
- FFIMYQQAUHRWHM-UHFFFAOYSA-N 5-methyl-8-propoxy-3-thiophen-3-yl-1h-quinolin-4-one Chemical compound CCCOC1=CC=C(C)C(C2=O)=C1NC=C2C=1C=CSC=1 FFIMYQQAUHRWHM-UHFFFAOYSA-N 0.000 description 1
- HJSSCBFMNMECFX-UHFFFAOYSA-N 6-fluoro-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC(F)=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 HJSSCBFMNMECFX-UHFFFAOYSA-N 0.000 description 1
- ZXBCRLXPAPIFHW-UHFFFAOYSA-N 6-imidazol-1-yl-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=CC(N2C=NC=C2)=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 ZXBCRLXPAPIFHW-UHFFFAOYSA-N 0.000 description 1
- UCXZEZYLWNMVDB-UHFFFAOYSA-N 7-fluoro-3-(4-methoxyphenyl)-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=C(F)C=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 UCXZEZYLWNMVDB-UHFFFAOYSA-N 0.000 description 1
- LATBNRJPKHKHBQ-UHFFFAOYSA-N 7-methoxy-3-(4-methoxyphenyl)-5-methyl-8-propoxy-1h-quinolin-4-one Chemical compound CCCOC1=C(OC)C=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 LATBNRJPKHKHBQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- YSPIEOUPRHSDHV-UHFFFAOYSA-N 8-(1-benzothiophen-2-yl)-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C=3SC4=CC=CC=C4C=3)C=CC(C)=C2C1=O YSPIEOUPRHSDHV-UHFFFAOYSA-N 0.000 description 1
- XEFNVLBATATCAJ-UHFFFAOYSA-N 8-(2-ethylimidazol-1-yl)-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound CCC1=NC=CN1C1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 XEFNVLBATATCAJ-UHFFFAOYSA-N 0.000 description 1
- LTIVWGWPIGPYNV-UHFFFAOYSA-N 8-(azepan-1-yl)-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(N3CCCCCC3)C=CC(C)=C2C1=O LTIVWGWPIGPYNV-UHFFFAOYSA-N 0.000 description 1
- CPDQQKOQWJLHOP-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(2,4-dichlorophenyl)-5-hydroxy-1h-quinolin-4-one Chemical compound C1=2NC=C(C=3C(=CC(Cl)=CC=3)Cl)C(=O)C=2C(O)=CC=C1OCC1CC1 CPDQQKOQWJLHOP-UHFFFAOYSA-N 0.000 description 1
- SXBMQFNHMBRKKY-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(2,4-dichlorophenyl)-5-methoxy-1h-quinolin-4-one Chemical compound C1=2NC=C(C=3C(=CC(Cl)=CC=3)Cl)C(=O)C=2C(OC)=CC=C1OCC1CC1 SXBMQFNHMBRKKY-UHFFFAOYSA-N 0.000 description 1
- JRIXZYJQHVQQTJ-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(2-fluoro-4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound FC1=CC(OC)=CC=C1C(C(C1=C(C)C=C2)=O)=CNC1=C2OCC1CC1 JRIXZYJQHVQQTJ-UHFFFAOYSA-N 0.000 description 1
- IIPZXGZMQIOURM-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(4-methoxyphenyl)-5,6-dimethyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=C(C)C(C)=C2)=O)=CNC1=C2OCC1CC1 IIPZXGZMQIOURM-UHFFFAOYSA-N 0.000 description 1
- QMXXFDIKWORYIN-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=C(C)C=C2)=O)=CNC1=C2OCC1CC1 QMXXFDIKWORYIN-UHFFFAOYSA-N 0.000 description 1
- LIBYMRJZRAISPY-UHFFFAOYSA-N 8-(cyclopropylmethoxy)-3-(furan-2-yl)-5-methoxy-2-methyl-1h-quinolin-4-one Chemical compound C1=2NC(C)=C(C=3OC=CC=3)C(=O)C=2C(OC)=CC=C1OCC1CC1 LIBYMRJZRAISPY-UHFFFAOYSA-N 0.000 description 1
- YLRYDORWETWFBB-UHFFFAOYSA-N 8-(furan-2-yl)-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(C=3OC=CC=3)C=CC(C)=C2C1=O YLRYDORWETWFBB-UHFFFAOYSA-N 0.000 description 1
- QVQIUQXZVUIRGG-UHFFFAOYSA-N 8-[2-methoxyethyl(methyl)amino]-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one;hydrochloride Chemical compound Cl.COCCN(C)C1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 QVQIUQXZVUIRGG-UHFFFAOYSA-N 0.000 description 1
- IEIRMRGPIYVSII-UHFFFAOYSA-N 8-bromo-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CNC2=C(Br)C=CC(C)=C2C1=O IEIRMRGPIYVSII-UHFFFAOYSA-N 0.000 description 1
- WOYSBHJMCJLCII-UHFFFAOYSA-N 8-butyl-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound CCCCC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 WOYSBHJMCJLCII-UHFFFAOYSA-N 0.000 description 1
- GQZAYAWXMGTXCE-UHFFFAOYSA-N 8-butyl-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound CCCCC1=CC=C(C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 GQZAYAWXMGTXCE-UHFFFAOYSA-N 0.000 description 1
- FSDDVEJVOIHMBK-UHFFFAOYSA-N 8-butyl-3-(4-methoxyphenyl)-n,n-dimethyl-4-oxo-1h-quinoline-5-carboxamide Chemical compound CCCCC1=CC=C(C(=O)N(C)C)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 FSDDVEJVOIHMBK-UHFFFAOYSA-N 0.000 description 1
- OGCMTMSWLHDGRL-UHFFFAOYSA-N 8-chloro-3-(4-methoxyphenyl)-5-propoxy-1h-quinolin-4-one Chemical compound O=C1C=2C(OCCC)=CC=C(Cl)C=2NC=C1C1=CC=C(OC)C=C1 OGCMTMSWLHDGRL-UHFFFAOYSA-N 0.000 description 1
- ZVZAZEGRPWUEHZ-UHFFFAOYSA-N 8-cyclopentyloxy-3-(2,4-dichlorophenyl)-5-hydroxy-1h-quinolin-4-one Chemical compound C1=2NC=C(C=3C(=CC(Cl)=CC=3)Cl)C(=O)C=2C(O)=CC=C1OC1CCCC1 ZVZAZEGRPWUEHZ-UHFFFAOYSA-N 0.000 description 1
- WSXVINKYBPFLKM-UHFFFAOYSA-N 8-cyclopentyloxy-3-(2,4-dichlorophenyl)-5-methoxy-1h-quinolin-4-one Chemical compound C1=2NC=C(C=3C(=CC(Cl)=CC=3)Cl)C(=O)C=2C(OC)=CC=C1OC1CCCC1 WSXVINKYBPFLKM-UHFFFAOYSA-N 0.000 description 1
- DRSVQBGXVQZBGX-UHFFFAOYSA-N 8-cyclopentyloxy-3-(4-methoxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=C(C)C=C2)=O)=CNC1=C2OC1CCCC1 DRSVQBGXVQZBGX-UHFFFAOYSA-N 0.000 description 1
- BCTBFVCSUXVMDK-UHFFFAOYSA-N 8-cyclopentyloxy-5-ethoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound C1=2NC=C(C=3C=CC(OC)=CC=3)C(=O)C=2C(OCC)=CC=C1OC1CCCC1 BCTBFVCSUXVMDK-UHFFFAOYSA-N 0.000 description 1
- ZQLQYKHGEOIPLO-UHFFFAOYSA-N 8-cyclopentyloxy-5-methoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound C1=CC(OC)=CC=C1C(C(C1=C(OC)C=C2)=O)=CNC1=C2OC1CCCC1 ZQLQYKHGEOIPLO-UHFFFAOYSA-N 0.000 description 1
- MGVNPMWKGWLGEV-UHFFFAOYSA-N 8-ethoxy-5-methoxy-3-(4-methoxyphenyl)-1h-quinolin-4-one Chemical compound CCOC1=CC=C(OC)C(C2=O)=C1NC=C2C1=CC=C(OC)C=C1 MGVNPMWKGWLGEV-UHFFFAOYSA-N 0.000 description 1
- JHQXIJLMHZBCCL-UHFFFAOYSA-N 8-hydroxy-3-(4-hydroxyphenyl)-5-methyl-1h-quinolin-4-one Chemical compound O=C1C=2C(C)=CC=C(O)C=2NC=C1C1=CC=C(O)C=C1 JHQXIJLMHZBCCL-UHFFFAOYSA-N 0.000 description 1
- ZHKGCEQSTDOWQY-UHFFFAOYSA-N 8-propoxy-3-(3,4,5-trimethoxyphenyl)-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC(OC)=C(OC)C(OC)=C1 ZHKGCEQSTDOWQY-UHFFFAOYSA-N 0.000 description 1
- DYBCBDHZVDLBKS-UHFFFAOYSA-N 8-propoxy-3-[2-(trifluoromethyl)phenyl]-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=CC=C1C(F)(F)F DYBCBDHZVDLBKS-UHFFFAOYSA-N 0.000 description 1
- KANGUTIEGXKIQS-UHFFFAOYSA-N 8-propoxy-3-pyridin-4-yl-1h-quinolin-4-one Chemical compound CCCOC1=CC=CC(C2=O)=C1NC=C2C1=CC=NC=C1 KANGUTIEGXKIQS-UHFFFAOYSA-N 0.000 description 1
- RYBYZMQZDJJYJC-UHFFFAOYSA-N 8-propyl-3-[4-(trifluoromethoxy)phenyl]-1h-quinolin-4-one Chemical compound CCCC1=CC=CC(C2=O)=C1NC=C2C1=CC=C(OC(F)(F)F)C=C1 RYBYZMQZDJJYJC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000013824 Acidemia Diseases 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 108010074725 Alpha,alpha-trehalose phosphorylase Proteins 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 241000586542 Aonidiella citrina Species 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UVGUXVZMWPGOPP-UHFFFAOYSA-N C(C)OC(CC1=CC=C(C=C1)OC)=O.C(C)OC(C(=CO)C1=CC=C(C=C1)OC)=O Chemical compound C(C)OC(CC1=CC=C(C=C1)OC)=O.C(C)OC(C(=CO)C1=CC=C(C=C1)OC)=O UVGUXVZMWPGOPP-UHFFFAOYSA-N 0.000 description 1
- DVVKOGYTZOZGHZ-UHFFFAOYSA-N CC1=CC(=C(C=C1)OCCC)[N+](=O)[O-].CC=1C=CC(=C(N)C1)OCCC Chemical compound CC1=CC(=C(C=C1)OCCC)[N+](=O)[O-].CC=1C=CC(=C(N)C1)OCCC DVVKOGYTZOZGHZ-UHFFFAOYSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- FMGYKKMPNATWHP-UHFFFAOYSA-N Cyperquat Chemical compound C1=C[N+](C)=CC=C1C1=CC=CC=C1 FMGYKKMPNATWHP-UHFFFAOYSA-N 0.000 description 1
- 208000002155 Cytochrome-c Oxidase Deficiency Diseases 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 229940081615 DOPA decarboxylase inhibitor Drugs 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000002251 Dissecting Aneurysm Diseases 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000027534 Emotional disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000004552 Lacunar Stroke Diseases 0.000 description 1
- 206010051078 Lacunar infarction Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 206010024612 Lipoma Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- 239000012580 N-2 Supplement Substances 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- 206010071390 Resting tremor Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002164 acetylcholinergic effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 206010002895 aortic dissection Diseases 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 229940039856 aricept Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000001269 cardiogenic effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000002060 circadian Effects 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- 208000031513 cyst Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000000534 dopa decarboxylase inhibitor Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 229950009041 edaravone Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 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
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 108091008147 housekeeping proteins Proteins 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([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
- 229940039009 isoproterenol Drugs 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910000032 lithium hydrogen carbonate Inorganic materials 0.000 description 1
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 206010028320 muscle necrosis Diseases 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- WKSFGKSRWFFTCU-UHFFFAOYSA-N n-[5,8-diethoxy-3-(4-methoxyphenyl)-4-oxo-1h-quinolin-6-yl]benzamide Chemical compound CCOC=1C(C(C(C=2C=CC(OC)=CC=2)=CN2)=O)=C2C(OCC)=CC=1NC(=O)C1=CC=CC=C1 WKSFGKSRWFFTCU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000033510 neuroaxonal dystrophy Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000001898 pallidal effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 125000005005 perfluorohexyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction 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
- 229940126585 therapeutic drug Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000004026 tunica intima Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Psychology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Nutrition Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
R1は、水素、低級アルキル基又はシクロC3-C8アルキル低級アルキル基を示す。
R2は、水素又は低級アルキル基を示す。
R3は、フェニル基、ナフチル基、ピリジル基、フリル基、チエニル基、インドリル基、ベンゾジオキソリル基又はベンゾチエニル基を示す。
ここで、上記R3で示される芳香環及び複素環上には、下記(1)〜(7)からなる群から選ばれた少なくとも1つの基が置換していてもよい:
(1)低級アルキル基、
(2)ハロゲン置換低級アルキル基、
(3)ヒドロキシ基、
(4)低級アルコキシ基、
(5)ハロゲン置換低級アルコキシ基ならびに、
(6)フェニル基(ここで、フェニル基上に低級アルキル基及び低級アルコキシ基からなる群から選ばれた基を1個以上有していてもよい)
(7)ハロゲンからなる群から選ばれた基を1個以上有していてもよい
R4は、水素、低級アルキル基、ハロゲン置換低級アルキル基、ヒドロキシ基、低級アルコキシ基、低級アルコキシ低級アルキル基、フェニル基、シクロC3-C8アルキル基又は低級アルキル基を1個又は2個有していてもよいカルバモイル基を示す。
R5は水素、低級アルキル基、ハロゲン、低級アルコキシ基、ベンゾイルアミノ又はイミダゾリル基を示す。
R6は、水素、ハロゲン、低級アルキル基、ヒドロキシ基又は低級アルコキシ基を示す。
R7は、下記(1)〜(19)のいずれかの基を示す。
(1)水素、
(2)ヒドロキシ基、
(3)低級アルキル基、
(4)低級アルコキシ基、
(5)フェノキシ基、
(6)シクロC3-C8アルキルオキシ基、
(7)ハロゲン、
(8)低級アルキルチオ基、
(9)アミノ基(ここで、アミノ基上に低級アルキル基、低級アルコキシ低級アルキル基及びシクロC3-C8アルキル基からなる群から選ばれた基を1個又は2個有していてもよい)
(10)低級アルキル基を1個又は2個有していてもよいカルバモイル基、
(11)ピロリジニル基、
(12)アゼパニル基、
(13)モルホリニル基、
(14)低級アルキル基を1個又は2個有していてもよいピペラジニル基、
(15)低級アルキル基を1個又は2個有していてもよいイミダゾリル基、
(16)フリル基、
(17)チエニル基、
(18)ベンゾチエニル基、
(19)ピロリジニルカルボニル基]
で表されるキノロン化合物又はその塩を有効成分として含有する、神経変性疾患、神経機能の障害に伴う疾患又はミトコンドリア機能の低下に伴う疾患の治療及び/又は予防剤。
[反応式−1]
一般式(3)において、R8で示される低級アルコキシ基は前記に示された定義と同じである。
[反応式−2]
一般式(6)において、R9で示される低級アルコキシ基は、前記に示された定義と同じである。
上記のような、4−キノロン化合物と4−ヒドロキシキノリン化合物との間のこの種の互変異性は技術上周知であり、両互変異性体が平衡しており相互に変換し得る状態にあることは当業者には明らかである。
4−メチル−2−ニトロ−1−プロポキシベンゼン
4−メチル−2−ニトロフェノール4.0g(26.1ミリモル)のN,N−ジメチルホルムアミド(DMF)溶液(10ml)に炭酸カリウム5.21g(37.7ミリモル)及び1−ヨードプロパン5.80g(34.1ミリモル)のDMF溶液(4ml)を加え、混合物を室温で48時間撹拌した。反応液に水を加え、得られる混合物を酢酸エチルで抽出した。有機層を飽和食塩水で2回洗浄し、減圧下に濃縮した。残渣をシリカゲルカラムクロマトグラフィー(n−ヘキサン:酢酸エチル=9:1)で精製した。精製物を減圧下に濃縮して淡黄色油状物の4−メチル−2−ニトロ−1−プロポキシベンゼン4.23g(収率83%)を得た。
1H−NMR (CDCl3) δppm : 1.05 (3H, t, J=7.4Hz), 1.80−1.86 (2H, m), 2.33 (3H, s), 4.02 (2H, t, J=6.4Hz), 6.95 (1H, d, J=8.5Hz), 7.29 (1H, d, J=8.5Hz), 7.62 (1H, s)。
5−メチル−2−プロポキシアニリン
4−メチル−2−ニトロ−1−プロポキシベンゼン2.0g(10.2ミリモル)及び5%パラジウム炭素700mgをエタノール30mlに加えて、室温常圧で接触還元した。触媒をセライト濾過して除去し、濾液を減圧下に濃縮した。残渣をジクロロメタンに溶解後、無水硫酸マグネシウムで乾燥した。得られた乾燥物を減圧下に濃縮して茶褐色油状物の5−メチル−2−プロポキシアニリン1.49g(収率89%)を得た。
1H−NMR (CDCl3 ) δppm : 1.05 (3H, t, J=7.4Hz), 1.76−1.86 (2H, m), 2.21 (3H, s), 3.73 (2H, brs), 3.91 (2H, t, J=6.5Hz), 6.49−6.50 (1H, m), 6.54 (1H, s), 6.66 (1H, d, J=8.0Hz)。
α−(ヒドロキシメチレン)−4−メトキシフェニル酢酸エチルエステル
4−メトキシフェニル酢酸エチルエステル2.0g(10.3ミリモル)のベンゼン溶液(10ml)に氷冷下、水素化ナトリウム(60%油性)467mg(11.7ミリモル)を加え、混合物を室温で5分間撹拌した。攪拌後の混合物を再び氷冷し、ぎ酸エチル1.02ml(12.6ミリモル)を加え、室温で3時間撹拌した。氷冷下、反応液に水及び酢酸エチルを加えた後、2N−塩酸6mlを加え、分液した。有機層を減圧下に濃縮し、残渣をシリカゲルカラムクロマトグラフィー(n−ヘキサン:酢酸エチル=4:1)で精製した。精製物を減圧下に濃縮して微赤褐色油状物のα−(ヒドロキシメチレン)−4−メトキシフェニル酢酸エチルエステル1.97g(収率86%)を得た。得られた目的物を窒素置換して冷凍庫に保管した。
1H−NMR (CDCl3 ) δppm : 1.28 (3H, t, J=7.1 Hz), 3.81 (3H, s), 4.28 (2H, q, J=7.1 Hz), 6.87 (2H, d, J=8.8Hz), 7.16−7.26 (3H, m), 12.02 (1H, d, J=12.5Hz)。
5−メチル−2−プロポキシアニリン1.49g(9.0ミリモル)及びα−(ヒドロキシメチレン)−4−メトキシフェニル酢酸エチルエステル2.00g(9.0ミリモル)のベンゼン溶液(50ml)に、270mgのアンバーリスト15(シグマ アルドリッチ)を加え、ディーン−スターク(Dean−Stark)トラップを用いて混合物を6時間、加熱還流下撹拌した。反応混合物を室温まで冷却し、濾過して樹脂を除去し、濾液を減圧下に濃縮した。残渣にジフェニルエーテル2.5mlを加え、混合物をマントルヒーターで加熱し、還流下50分間撹拌した。反応液を室温まで冷却後、直接シリカゲルカラムクロマトグラフィー(ジクロロメタン:メタノール=80:1→60:1)で精製した。精製物を減圧下に濃縮し、残渣を酢酸エチルから再結晶して淡黄色鱗片状晶の3−(4−メトキシフェニル)−5−メチル−8−プロポキシ−1H−キノリン−4−オン600mg(収率21%)を得た。
融点 192−193℃。
白色粉末
融点 129-131℃。
黄色粉末
融点 231-233℃。
淡褐色粉末
1H-NMR (DMSO-d6 ) δppm : 1.35 (3H, t, J=6.8Hz), 3.76 (3H, s), 4.23 (2H, q, J=6.9Hz), 6.84-6.96 (4H, m), 7.64 (2H, d, J=8.6Hz), 8.09 (1H, s), 8.11 (1H, d, J=8.8Hz), 10.33 (1H, s)。
淡黄色粉末
1H-NMR (DMSO-d6 ) δppm : 3.70 (3H, s), 3.76 (3H, s), 3.86 (3H, s), 3.93 (3H, s), 6.48 (1H, s), 6.95 (2H, d, J=8.8Hz), 7.59 (2H, d, J=8.8Hz), 8.22 (1H, s) 11.40 (1H, brs)。
淡褐色粉末
1H-NMR (DMSO-d6 ) δppm : 0.90 (3H, t, J=7.2Hz), 1.34-1.39 (2H, m), 1.55-1.59 (2H, m), 2.86 (2H, t, J=7.5Hz), 3.76 (3H, s), 6.95 (2H, d, J=8.5Hz), 7.25 (1H, t, J=7.7Hz), 7.46 (1H, d, J=6.9Hz), 7.62 (2H, d, J=8.5Hz), 7.92 (1H, s), 8.08 (1H, d, J=8.0Hz), 11.39 (1H, brs)。
白色粉末
1H-NMR (DMSO-d6 ) δppm : 0.94 (3H, t, J=7.2Hz), 1.59-1.64 (2H, m), 2.83 (2H, t, J=7.5Hz), 3.75 (3H, s), 6.93-6.95 (2H, m), 7.25 (1H, t, J=7.8Hz), 7.46 (1H, d, J=6.0Hz), 7.60-7.61 (2H, m), 7.92 (1H, s), 8.07-8.09 (1H, m), 11.40 (1H, brs)。
淡黄色粉末
1H-NMR (DMSO-d6 ) δppm : 0.96 (3H, t, J=7.2Hz), 1.59-1.66 (2H, m), 2.85 (2H, t, J=7.6Hz), 7.27 (1H, t, J=7.9Hz), 7.36 (2H, d, J=8.7Hz), 7.49 (1H, d, J=7.0Hz), 7.83 (2H, d, J=8.7Hz), 8.02 (1H, s), 8.09-8.10 (1H, m), 11.47 (1H, brs)。
白色粉末
1H-NMR (DMSO-d6 ) δppm : 0.95 (3H, t, J=7.2Hz), 1.58-1.65 (2H, m), 2.84 (2H, t, J=7.6Hz), 7.27 (1H, d, J=7.9Hz), 7.48 (1H, d, J=7.1Hz), 7.55 (2H, d, J=8.5Hz), 7.67 (2H, d, J=8.5Hz), 8.00 (1H, s), 8.08-8.09 (1H, m), 11.46 (1H, brs)。
淡褐色粉末
1H-NMR (DMSO-d6 ) δppm : 0.95 (3H, t, J=7.2Hz), 1.59-1.66 (2H, m), 2.85 (2H, t, J=7.6Hz), 3.81 (3H, s), 7.00 (2H, d, J=8.7Hz), 7.28 (1H, t, J=8.5Hz), 7.48 (1H, d, J=7.1Hz), 7.60-7.7.64 (4H, m), 7.76 (2H, d, J=8.2Hz), 8.02 (1H, s), 8.11 (1H, d, J=8.1Hz), 11.45 (1H, brs)。
白色粉末
1H-NMR (DMSO-d6 ) δppm : 1.37 (3H, t, J=6.9Hz), 3.91 (3H, s), 4.34 (2H, q, J=7.0Hz), 7.01-7.04 (2H, m), 7.54 (2H, d, J=8.4Hz), 7.69 (2H, d, J=8.4Hz), 8.20 (1H, d, J=8.8Hz), 8.24 (1H, s)。
白色粉末
1H-NMR (DMSO-d6 ) δppm : 1.38 (3H, t, J=7.0Hz), 3.91 (3H, s), 4.35 (2H, q, J=7.0Hz), 7.01-7.05 (2H, m), 7.34 (1H, t, J=7.4Hz), 7.45 (2H, t, J=7.6Hz), 7.65-7.68 (4H, m), 7.81 (2H, d, J=8.3Hz), 8.22-8.25 (2H, m)。
淡褐色粉末
融点 223-224℃。
淡黄色粉末
融点 210−211℃。
淡褐色粉末
融点 259−260℃。
淡褐色粉末
融点 231−232℃。
淡褐色アモルファス
1H-NMR (DMSO-d6 ) δppm : 1.04 (3H, t, J=7.3Hz), 1.78-1.90 (2H, m), 3.67 (3H, s), 3.84 (6H, s), 4.12 (2H, t, J=6.4Hz), 7.00 (2H, s), 7.17-7.26 (2H, m), 7.74 (1H, d, J=6.7Hz), 7.99 (1H, d, J=6.3Hz), 11.47 (1H, d, J=6.2Hz)。
淡褐色粉末
融点 250−251℃。
実施例19
淡黄色粉末
融点 214−215℃。
淡黄色粉末
融点 193−194℃。
淡灰色粉末
融点 113−114℃。
淡褐色粉末
融点 186−187℃。
淡黄色粉末
融点 174−175℃。
淡黄色粉末
融点 220−221℃。
淡黄色粉末
融点 182−183℃。
淡黄色粉末
融点 159−160℃。
緑色粉末
融点 189℃。
淡褐色粉末
融点 193℃。
淡橙色粉末
融点 230℃。
淡褐色粉末
融点 250℃。
淡黄色粉末
融点 175℃。
白色粉末
融点 224℃。
淡褐色粉末
融点 160℃。
淡黄色粉末
融点 153−154℃。
淡褐色粉末
融点 120−121℃。
淡黄色粉末
融点 161−162℃。
淡褐色粉末
融点 195−196℃。
白色粉末
融点 125℃。
白色粉末
融点 218−220℃。
白色粉末
融点 239−241℃。
淡黄色粉末
融点 253−255℃。
淡黄色粉末
融点 145−148℃。
淡黄色粉末
融点 179−180℃。
淡黄色粉末
融点 255−256℃。
淡黄色粉末
融点 117−119℃。
淡黄色粉末
融点 213−214℃。
淡黄色粉末
融点 242−244℃。
淡黄色粉末
融点 160−161℃。
淡黄色粉末
融点 169−170℃。
淡黄色粉末
融点 201−202℃。
淡黄色粉末
融点 130−133℃。
白色粉末
融点 221−223℃。
淡黄色粉末
融点 170−171℃。
淡黄色粉末
融点 200−203℃。
淡黄色粉末
融点 107−108℃。
淡黄色粉末
融点 81−84℃。
淡黄色粉末
融点 103−106℃。
淡褐色粉末
融点 104−107℃。
淡橙色粉末
融点 189−193℃。
淡褐色粉末
融点 110−115℃。
薄緑色粉末
融点 104−105℃。
淡褐色粉末
融点 106−109℃。
淡褐色粉末
融点 80−82℃。
淡褐色粉末
融点 81−83℃。
白色粉末
融点 168−170℃。
淡黄色粉末
融点 90−92℃。
淡黄色粉末
融点 196−198℃。
淡黄色粉末
融点 177−178℃。
白色粉末
融点 182−183℃。
淡黄色粉末
融点 132−135℃。
淡黄色粉末
融点 258−260℃。
白色粉末
融点 159−161℃。
淡褐色粉末
融点 260−263℃。
白色粉末
融点 265−267℃。
淡黄色粉末
融点 270−275℃(分解)。
淡黄色粉末
融点 186−188℃。
淡褐色粉末
融点 214-215℃。
白色粉末
融点 191-192℃。
白色粉末
融点 198−199℃。
淡黄色粉末
融点 156−158℃。
淡黄色粉末
融点 145−147℃。
淡黄色粉末
融点 198−200℃。
淡褐色粉末
融点 99−101℃。
黄色粉末
融点 249−250℃。
淡褐色粉末
融点 236−237℃。
淡黄色粉末
融点 185−186℃。
淡灰色粉末
融点 218−220℃。
淡褐色粉末
融点 212−214℃。
黄色粉末
融点 158−160℃。
淡褐色粉末
融点 193−195℃。
淡黄色粉末
融点 237−239℃。
白色粉末
融点 100-101℃。
黄緑色粉末
融点 213−215℃。
淡黄色粉末
融点 232−234℃。
淡橙色粉末
融点 112-113℃。
淡黄色粉末
融点 129-131℃。
白色粉末
融点 189-190℃。
白色粉末
融点 229-231℃。
白色粉末
融点 186-187℃。
橙色粉末
融点 197-199℃。
淡黄色粉末
融点 90-93℃。
白色粉末
融点 111−113℃。
白色粉末
融点 186−187℃。
白色粉末
融点 266−268℃。
淡褐色粉末
融点 254−256℃。
黄色粉末
融点 154−155℃。
黄色粉末
融点 163−165℃。
淡黄色粉末
融点 204−206℃。
淡黄色粉末
融点 189-190℃。
1−メチル−4−フェニルピリジニウム(MPP + )処置ヒト神経芽細胞腫株SH−SY5Yを用いたミトコンドリア機能改善作用の測定
MPP+処置によりミトコンドリア機能が障害されたヒト神経芽細胞腫株SH−SY5Y [Bollimuntha S.ら、J Biol Chem, 280, 2132−2140 (2005)及びShang T.ら、J Biol Chem, 280, 34644−34653 (2005)] において、化合物添加後のアラマーブルー蛍光色素を用いたミトコンドリア酸化還元活性測定値を指標 [Nakai M.ら、Exp Neurol, 179, 103−110 (2003)]に、ミトコンドリア機能改善作用を評価した。
1−メチル−4−フェニル1,2,3,6−テトラハイドロピリジン(MPTP)処置C57BL/6マウスを用いたドパミン神経保護作用の測定
MPTP処置によりドパミン作動性神経が傷害されたマウス[Chan P.ら、J Neurochem, 57, 348−351 (1991)]を用い、化合物投与後の脳線条体部位におけるドパミン神経のマーカー蛋白であるチロシン水酸化酵素(TH)並びにドパミントランスポーター(DAT)の蛋白レベルと同部位におけるドパミン含量を指標[Mori A.ら、Neurosci Res, 51, 265−274 (2005)]に、ドパミン神経保護作用を評価した。
Claims (5)
- 一般式(1)
R1は、水素を示す。
R2は、水素又は低級アルキル基を示す。
R3は、フェニル基、ナフチル基、ピリジル基、フリル基、チエニル基、インドリル基、ベンゾジオキソリル基又はベンゾチエニル基を示す。
ここで、上記R3で示される芳香環及び複素環上には、下記(1)、(2)及び(4)〜(7)からなる群から選ばれた少なくとも1つの基が置換していてもよい:
(1)低級アルキル基、
(2)ハロゲン置換低級アルキル基、
(4)低級アルコキシ基、
(5)ハロゲン置換低級アルコキシ基ならびに、
(6)フェニル基(ここで、フェニル基上に低級アルキル基及び低級アルコキシ基からなる群から選ばれた基を1個以上有していてもよい)
(7)ハロゲンからなる群から選ばれた基を1個以上有していてもよい
R4は、水素、低級アルキル基、ハロゲン置換低級アルキル基、低級アルコキシ基、低級アルコキシ低級アルキル基、フェニル基、シクロC3-C8アルキル基又は低級アルキル基を1個又は2個有していてもよいカルバモイル基を示す。
R5は水素、低級アルキル基、ハロゲン、低級アルコキシ基、ベンゾイルアミノ又はイミダゾリル基を示す。
R6は、水素、ハロゲン、低級アルキル基又は低級アルコキシ基を示す。
R7は、下記(3)〜(19)のいずれかの基を示す。
(3)低級アルキル基、
(4)低級アルコキシ基、
(5)フェノキシ基、
(6)シクロC3-C8アルキルオキシ基、
(7)ハロゲン、
(8)低級アルキルチオ基、
(9)アミノ基(ここで、アミノ基上に低級アルキル基、低級アルコキシ低級アルキル基及びシクロC3-C8アルキル基からなる群から選ばれた基を1個又は2個有していてもよい)
(10)低級アルキル基を1個又は2個有していてもよいカルバモイル基、
(11)ピロリジニル基、
(12)アゼパニル基、
(13)モルホリニル基、
(14)低級アルキル基を1個又は2個有していてもよいピペラジニル基、
(15)低級アルキル基を1個又は2個有していてもよいイミダゾリル基、
(16)フリル基、
(17)チエニル基、
(18)ベンゾチエニル基、
(19)ピロリジニルカルボニル基]
で表されるキノロン化合物又はその塩を有効成分として含有する、神経変性疾患、神経機能の障害に伴う疾患又はミトコンドリア機能の低下に伴う疾患の治療及び/又は予防剤。 - 神経変性疾患が、パーキンソン病、パーキンソン症候群、若年性パーキンソンニズム、線条体黒質変性症、進行性核上性麻痺、純粋無動症、アルツハイマー病、ピック病、プリオン病、大脳皮質基底核変性症、びまん性レビー小体病、ハンチントン病、有棘赤血球舞踏病、良性遺伝性舞踏病、発作性舞踏アテトーゼ、本態性振戦、本態性ミオクローヌス、ジル・ド・ラ・トゥレット症候群、レット症候群、変性性バリズム、変形性筋ジストニー、アテトーゼ、痙性斜頸、メイジ症候群、脳性麻痺、ウィルソン病、瀬川病、ハレルフォルデン・スパッツ症候群、神経軸索ジストロフィー、淡蒼球萎縮症、脊髄小脳変性症、皮質性小脳萎縮症、ホームズ型小脳萎縮症、オリーブ橋小脳萎縮症、遺伝性オリーブ橋小脳萎縮症、ジョセフ病、歯状核赤核淡蒼球ルイ体萎縮症、ゲルストマン・シュトロイスラー・シャインカ症候群、フリードライヒ運動失調症、ルシー・レヴィー症候群、メイ・ホワイト症候群、先天性小脳失調症、周期性遺伝性失調症、毛細血管拡張運動失調症、筋萎縮性側索硬化症、進行性球麻痺、脊髄性進行性筋萎縮症、球脊髄性筋萎縮症、ウェルドニッヒ・ホフマン病、クーゲルベルク・ウエランダー病、遺伝性痙性対麻痺、脊髄空洞症、延髄空洞症、アーノルド・キアリー奇形、スティフマン症候群、クリッペル・ファイル症候群、ファチオーロンド病、低位脊髄症、ダンディー・ウォーカー症候群、二分脊椎、シューグレン・ラーソン症候群、放射線脊髄症、加齢黄斑変性、ならびに脳梗塞及び脳出血から選ばれる脳卒中及び/またはそれに伴う機能不全もしくは神経脱落症状からなる群から選ばれる疾患である、請求項1に記載の治療及び/又は予防剤。
- 神経機能の障害に伴う疾患が、脊髄損傷、化学療法で誘発された神経障害、糖尿病性神経障害、放射性障害、ならびに多発性硬化症、急性散在性脳脊髄炎、横断性脊髄炎、進行性多巣性白質脳症、亜急性硬化症全脳炎、慢性炎症性脱髄性多発根神経炎及びギラン・バレー症候群から選ばれる脱髄疾患である、請求項1に記載の治療及び/又は予防剤。
- ミトコンドリア機能の低下に伴う疾患が、ピアソン症候群、糖尿病、難聴、悪性片頭痛、レーバー病、メラス(MELAS)、マーフ(MERRF)、マーフ/メラス重複症候群、NARP、純粋型ミオパチー、ミトコンドリア心筋症、ミオパチー、痴呆、胃腸運動失調、後天性鉄芽球性貧血、アミノグリコシド誘発性難聴、チトクロムb遺伝子変異による複合体III欠損症、対称性多発性脂肪腫症、運動失調、ミオクローヌス、網膜症、MNGIE、ANT1異常症、トウィンクル異常症、POLG異常症、反復性ミオグロビン尿症、SANDO、ARCO、複合体I欠損症、複合体II欠損症、視神経萎縮、複合体IV欠損重症乳児型、ミトコンドリアDNA欠乏症候群、リー脳症、慢性進行性外眼筋麻痺症候群(CPEO)、キーンズ・セイヤー症候群、脳症、乳酸血症、ミオグロビン尿、薬物誘発性ミトコンドリア病、統合失調症、大うつ病性障害、双極I型障害、双極II型障害、混合状態、気分変調性障害、非定型うつ病、季節性感情障害、産後うつ病、軽症うつ病、反復性短期うつ病性障害、難治性うつ病、慢性うつ病、重複うつ病及び急性腎不全である、請求項1に記載の治療及び/又は予防剤。
- 請求項1に記載の一般式(1)で表されるキノロン化合物又はその塩を有効成分として含有する、虚血性心疾患及び/またはそれに伴う機能不全、心不全、心筋症、大動脈乖離、免疫不全症、自己免疫疾患、膵不全、糖尿病、アテローム塞栓性腎疾患、多発性嚢胞腎、髄質嚢胞性疾患、腎皮質壊死、悪性腎硬化症、腎不全、肝性脳症、肝不全、慢性閉塞性肺疾患、肺塞栓症、気管支拡張症、珪肺症、黒色肺、特発性肺線維症、スティーブンス・ジョンソン症候群、中毒性表皮壊死症、筋ジストロフィ、クロストリジウム性筋肉壊死並びに大腿骨顆部骨壊死の疾患の治療及び/または予防剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010541367A JP5546463B2 (ja) | 2008-12-05 | 2009-12-04 | キノロン化合物を含む薬剤 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2008310716 | 2008-12-05 | ||
JP2008310716 | 2008-12-05 | ||
JP2010541367A JP5546463B2 (ja) | 2008-12-05 | 2009-12-04 | キノロン化合物を含む薬剤 |
PCT/JP2009/070383 WO2010064701A1 (ja) | 2008-12-05 | 2009-12-04 | キノロン化合物を含む薬剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2010064701A1 JPWO2010064701A1 (ja) | 2012-05-10 |
JP5546463B2 true JP5546463B2 (ja) | 2014-07-09 |
Family
ID=42233348
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010541367A Expired - Fee Related JP5546463B2 (ja) | 2008-12-05 | 2009-12-04 | キノロン化合物を含む薬剤 |
Country Status (8)
Country | Link |
---|---|
US (2) | US20110251180A1 (ja) |
EP (1) | EP2364706B1 (ja) |
JP (1) | JP5546463B2 (ja) |
KR (1) | KR20110096143A (ja) |
CN (1) | CN102238951A (ja) |
CA (1) | CA2745015A1 (ja) |
ES (1) | ES2546507T3 (ja) |
WO (1) | WO2010064701A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014001227A (ja) * | 2008-12-05 | 2014-01-09 | Otsuka Pharmaceut Co Ltd | キノロン化合物及び医薬組成物 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI366565B (en) | 2007-06-06 | 2012-06-21 | Otsuka Pharma Co Ltd | Quinolone compound and pharmaceutical composition |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998017662A1 (en) * | 1996-10-18 | 1998-04-30 | Novartis Ag | Phenyl-substituted bicyclic heterocyclyl derivatives and their use |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1296985B1 (it) * | 1997-12-19 | 1999-08-03 | Zambon Spa | Derivati benzazinici inibitori della fosfodiesterasi 4 |
FR2797444B1 (fr) * | 1999-08-13 | 2003-02-07 | Lafon Labor | Compositions pharmaceutiques comprenant des 4-quinolones |
FR2813791B1 (fr) | 2000-09-14 | 2004-03-12 | Lafon Labor | Utilisation de 2- et 4-quinolones pour inhiber la neo-proliferation intimale |
TWI366565B (en) * | 2007-06-06 | 2012-06-21 | Otsuka Pharma Co Ltd | Quinolone compound and pharmaceutical composition |
WO2009053799A1 (en) * | 2007-10-24 | 2009-04-30 | Glenmark Pharmaceuticals, S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
-
2009
- 2009-12-04 US US13/128,803 patent/US20110251180A1/en not_active Abandoned
- 2009-12-04 JP JP2010541367A patent/JP5546463B2/ja not_active Expired - Fee Related
- 2009-12-04 CN CN2009801486029A patent/CN102238951A/zh active Pending
- 2009-12-04 KR KR1020117015164A patent/KR20110096143A/ko not_active Application Discontinuation
- 2009-12-04 WO PCT/JP2009/070383 patent/WO2010064701A1/ja active Application Filing
- 2009-12-04 EP EP09830467.8A patent/EP2364706B1/en not_active Not-in-force
- 2009-12-04 ES ES09830467.8T patent/ES2546507T3/es active Active
- 2009-12-04 CA CA2745015A patent/CA2745015A1/en not_active Abandoned
-
2013
- 2013-03-28 US US13/852,196 patent/US20130217678A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998017662A1 (en) * | 1996-10-18 | 1998-04-30 | Novartis Ag | Phenyl-substituted bicyclic heterocyclyl derivatives and their use |
Non-Patent Citations (1)
Title |
---|
JPN6014003031; Bioorganic & Medicinal Chemistry Letters, June 2008,Vol.18,No.14,p.4092-4094 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014001227A (ja) * | 2008-12-05 | 2014-01-09 | Otsuka Pharmaceut Co Ltd | キノロン化合物及び医薬組成物 |
Also Published As
Publication number | Publication date |
---|---|
US20130217678A1 (en) | 2013-08-22 |
EP2364706A1 (en) | 2011-09-14 |
EP2364706A4 (en) | 2012-08-22 |
WO2010064701A1 (ja) | 2010-06-10 |
JPWO2010064701A1 (ja) | 2012-05-10 |
CN102238951A (zh) | 2011-11-09 |
US20110251180A1 (en) | 2011-10-13 |
CA2745015A1 (en) | 2010-06-10 |
EP2364706B1 (en) | 2015-07-29 |
ES2546507T3 (es) | 2015-09-24 |
KR20110096143A (ko) | 2011-08-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5063708B2 (ja) | キノロン化合物及び医薬組成物 | |
KR20140041583A (ko) | Lrrk2 키나제 활성의 억제제 | |
KR101278383B1 (ko) | 퀴놀론 화합물 및 제약 조성물 | |
JP5546463B2 (ja) | キノロン化合物を含む薬剤 | |
JP5769504B2 (ja) | 医薬 | |
JP5247667B2 (ja) | 医薬 | |
KR20220118483A (ko) | Oga 억제제 화합물 | |
WO2021110656A1 (en) | Oga inhibitor compounds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121120 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140128 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140328 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140422 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140513 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5546463 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |