JP2018511581A5 - - Google Patents

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Publication number

JP2018511581A5

JP2018511581A5 JP2017546676A JP2017546676A JP2018511581A5 JP 2018511581 A5 JP2018511581 A5 JP 2018511581A5 JP 2017546676 A JP2017546676 A JP 2017546676A JP 2017546676 A JP2017546676 A JP 2017546676A JP 2018511581 A5 JP2018511581 A5 JP 2018511581A5

Authority

JP

Japan

Prior art keywords

alkyl

aryl

fibrosis

substituted

disease

Prior art date

2016-03-08

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.)

Pending

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• 125000000217 alkyl group Chemical group 0.000 claims description 262
• -1 thiocarbamoyl Chemical group 0.000 claims description 218
• 108010051913 15-hydroxyprostaglandin dehydrogenase Proteins 0.000 claims description 156
• 102100030489 15-hydroxyprostaglandin dehydrogenase [NAD(+)] Human genes 0.000 claims description 156
• 125000003118 aryl group Chemical group 0.000 claims description 146
• 239000003112 inhibitor Substances 0.000 claims description 141
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 99
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 94
• 229910052739 hydrogen Inorganic materials 0.000 claims description 87
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 72
• 229910052757 nitrogen Inorganic materials 0.000 claims description 71
• 239000001257 hydrogen Substances 0.000 claims description 69
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 68
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
• 206010016654 Fibrosis Diseases 0.000 claims description 58
• 201000010099 disease Diseases 0.000 claims description 56
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 55
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 51
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
• 150000003839 salts Chemical class 0.000 claims description 47
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 45
• 125000006413 ring segment Chemical group 0.000 claims description 44
• 208000035475 disorder Diseases 0.000 claims description 42
• 230000004761 fibrosis Effects 0.000 claims description 41
• 125000004414 alkyl thio group Chemical group 0.000 claims description 38
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 37
• 125000001072 heteroaryl group Chemical group 0.000 claims description 36
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 35
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 35
• 125000003342 alkenyl group Chemical group 0.000 claims description 34
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 34
• 238000006243 chemical reaction Methods 0.000 claims description 34
• 230000003176 fibrotic effect Effects 0.000 claims description 34
• 229910019142 PO4 Inorganic materials 0.000 claims description 32
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 30
• 125000000304 alkynyl group Chemical group 0.000 claims description 30
• 210000001519 tissue Anatomy 0.000 claims description 30
• 102000008186 Collagen Human genes 0.000 claims description 29
• 108010035532 Collagen Proteins 0.000 claims description 29
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 229920001436 collagen Polymers 0.000 claims description 29
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• 229910052760 oxygen Inorganic materials 0.000 claims description 28
• 239000010452 phosphate Substances 0.000 claims description 28
• 125000003545 alkoxy group Chemical group 0.000 claims description 27
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 27
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 25
• 229910052717 sulfur Inorganic materials 0.000 claims description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 239000003814 drug Substances 0.000 claims description 22
• 108090000623 proteins and genes Proteins 0.000 claims description 22
• 125000003282 alkyl amino group Chemical group 0.000 claims description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
• 229910052801 chlorine Inorganic materials 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 21
• 210000000056 organ Anatomy 0.000 claims description 21
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
• 125000005110 aryl thio group Chemical group 0.000 claims description 20
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 20
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 20
• 125000003367 polycyclic group Chemical group 0.000 claims description 20
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 19
• 125000001769 aryl amino group Chemical group 0.000 claims description 19
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 19
• 229940079593 drug Drugs 0.000 claims description 19
• 210000004072 lung Anatomy 0.000 claims description 19
• 125000002950 monocyclic group Chemical group 0.000 claims description 19
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 19
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 18
• 229910052794 bromium Inorganic materials 0.000 claims description 18
• 230000007882 cirrhosis Effects 0.000 claims description 18
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 18
• 230000014509 gene expression Effects 0.000 claims description 18
• 229940124530 sulfonamide Drugs 0.000 claims description 18
• 150000003456 sulfonamides Chemical class 0.000 claims description 18
• 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims description 18
• 125000002252 acyl group Chemical group 0.000 claims description 17
• 125000004423 acyloxy group Chemical group 0.000 claims description 17
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 17
• 125000005277 alkyl imino group Chemical group 0.000 claims description 17
• 150000001413 amino acids Chemical class 0.000 claims description 17
• 125000004467 aryl imino group Chemical group 0.000 claims description 17
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 17
• 125000005163 aryl sulfanyl group Chemical group 0.000 claims description 17
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 17
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 17
• 125000004104 aryloxy group Chemical group 0.000 claims description 17
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 17
• 230000015572 biosynthetic process Effects 0.000 claims description 17
• 239000004202 carbamide Substances 0.000 claims description 17
• 235000013877 carbamide Nutrition 0.000 claims description 17
• 125000001651 cyanato group Chemical group [*]OC#N 0.000 claims description 17
• 230000008021 deposition Effects 0.000 claims description 17
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 17
• 125000001261 isocyanato group Chemical group *N=C=O 0.000 claims description 17
• 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 claims description 17
• 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 claims description 17
• RIFHJAODNHLCBH-UHFFFAOYSA-N methanethione Chemical group S=[CH] RIFHJAODNHLCBH-UHFFFAOYSA-N 0.000 claims description 17
• 125000000394 phosphonato group Chemical group [O-]P([O-])(*)=O 0.000 claims description 17
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 17
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 16
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 16
• 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 16
• 125000002579 carboxylato group Chemical group [O-]C(*)=O 0.000 claims description 16
• FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 claims description 16
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 16
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
• 239000000126 substance Substances 0.000 claims description 15
• 238000011282 treatment Methods 0.000 claims description 15
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• 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 14
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 14
• 210000002744 extracellular matrix Anatomy 0.000 claims description 14
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 14
• 102000004169 proteins and genes Human genes 0.000 claims description 14
• 206010039710 Scleroderma Diseases 0.000 claims description 12
• 108090000695 Cytokines Proteins 0.000 claims description 11
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• 238000012261 overproduction Methods 0.000 claims description 10
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• 208000006673 asthma Diseases 0.000 claims description 9
• 125000004122 cyclic group Chemical group 0.000 claims description 9
• 229910052740 iodine Inorganic materials 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 208000020832 chronic kidney disease Diseases 0.000 claims description 8
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• 239000011159 matrix material Substances 0.000 claims description 8
• 206010028537 myelofibrosis Diseases 0.000 claims description 8
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
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• 230000002159 abnormal effect Effects 0.000 claims description 7
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 7
• 208000033116 Asbestos intoxication Diseases 0.000 claims description 6
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 6
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 6
• 208000029523 Interstitial Lung disease Diseases 0.000 claims description 6
• 206010028594 Myocardial fibrosis Diseases 0.000 claims description 6
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 6
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• 239000000443 aerosol Substances 0.000 claims description 6
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• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
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• 241000193738 Bacillus anthracis Species 0.000 claims description 3
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• GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
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