JP7579253B2 - 甲状腺ホルモン受容体ベータアゴニスト化合物 - Google Patents

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Publication number

JP7579253B2

JP7579253B2 JP2021533405A JP2021533405A JP7579253B2 JP 7579253 B2 JP7579253 B2 JP 7579253B2 JP 2021533405 A JP2021533405 A JP 2021533405A JP 2021533405 A JP2021533405 A JP 2021533405A JP 7579253 B2 JP7579253 B2 JP 7579253B2

Authority

JP

Japan

Prior art keywords

substituted

methyl

alkyl

compound

oxo

Prior art date

2018-08-24

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.)

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• 150000001875 compounds Chemical class 0.000 title claims description 322
• 229940123876 Thyroid hormone receptor beta agonist Drugs 0.000 title 1
• 125000000623 heterocyclic group Chemical group 0.000 claims description 144
• -1 C 1 -C 4 alkyl Chemical group 0.000 claims description 111
• 125000000217 alkyl group Chemical group 0.000 claims description 90
• 150000003839 salts Chemical class 0.000 claims description 88
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 68
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
• 229910052757 nitrogen Inorganic materials 0.000 claims description 42
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 33
• 125000004429 atom Chemical group 0.000 claims description 28
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 239000008194 pharmaceutical composition Substances 0.000 claims description 25
• 125000005842 heteroatom Chemical group 0.000 claims description 23
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000000468 ketone group Chemical group 0.000 claims description 16
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
• 230000001404 mediated effect Effects 0.000 claims description 10
• 239000012453 solvate Substances 0.000 claims description 10
• 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 9
• 125000001475 halogen functional group Chemical group 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 150000001204 N-oxides Chemical class 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 572
• 239000000203 mixture Substances 0.000 description 388
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 245
• 235000019439 ethyl acetate Nutrition 0.000 description 211
• 239000000243 solution Substances 0.000 description 157
• 230000002829 reductive effect Effects 0.000 description 154
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
• 125000001072 heteroaryl group Chemical group 0.000 description 111
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 106
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 96
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
• 239000003208 petroleum Substances 0.000 description 96
• 239000011541 reaction mixture Substances 0.000 description 95
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 91
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 83
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 80
• 239000012267 brine Substances 0.000 description 80
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 80
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 77
• 238000012746 preparative thin layer chromatography Methods 0.000 description 77
• 238000004809 thin layer chromatography Methods 0.000 description 68
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 67
• 125000003118 aryl group Chemical group 0.000 description 67
• 238000005481 NMR spectroscopy Methods 0.000 description 66
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
• 238000005160 1H NMR spectroscopy Methods 0.000 description 57
• 125000000547 substituted alkyl group Chemical group 0.000 description 55
• 239000012074 organic phase Substances 0.000 description 54
• 238000000034 method Methods 0.000 description 52
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 51
• 125000003107 substituted aryl group Chemical group 0.000 description 51
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 50
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 48
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 44
• HDYZPOFPZYDBSF-UHFFFAOYSA-N 5-oxo-4H-1,2,4-oxadiazole-3-carbonyl chloride Chemical compound O=C1NC(=NO1)C(=O)Cl HDYZPOFPZYDBSF-UHFFFAOYSA-N 0.000 description 41
• 239000012044 organic layer Substances 0.000 description 40
• 238000002953 preparative HPLC Methods 0.000 description 39
• 125000003342 alkenyl group Chemical group 0.000 description 37
• 229910052739 hydrogen Inorganic materials 0.000 description 36
• 125000000304 alkynyl group Chemical group 0.000 description 35
• 239000001257 hydrogen Substances 0.000 description 35
• 239000012071 phase Substances 0.000 description 35
• 125000001424 substituent group Chemical group 0.000 description 35
• 125000005017 substituted alkenyl group Chemical group 0.000 description 34
• 125000004426 substituted alkynyl group Chemical group 0.000 description 34
• 229910052681 coesite Inorganic materials 0.000 description 33
• 229910052906 cristobalite Inorganic materials 0.000 description 33
• 239000000377 silicon dioxide Substances 0.000 description 33
• 235000012239 silicon dioxide Nutrition 0.000 description 33
• 229910052682 stishovite Inorganic materials 0.000 description 33
• 229910052905 tridymite Inorganic materials 0.000 description 33
• 125000003545 alkoxy group Chemical group 0.000 description 32
• 201000010099 disease Diseases 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 30
• 238000000746 purification Methods 0.000 description 30
• 229910052938 sodium sulfate Inorganic materials 0.000 description 30
• 235000011152 sodium sulphate Nutrition 0.000 description 30
• 229910004298 SiO 2 Inorganic materials 0.000 description 28
• 208000035475 disorder Diseases 0.000 description 28
• 150000002431 hydrogen Chemical class 0.000 description 28
• 125000005415 substituted alkoxy group Chemical group 0.000 description 27
• 238000006243 chemical reaction Methods 0.000 description 24
• 229910000027 potassium carbonate Inorganic materials 0.000 description 24
• 235000015320 potassium carbonate Nutrition 0.000 description 24
• 239000007858 starting material Substances 0.000 description 24
• 239000000725 suspension Substances 0.000 description 24
• 239000000047 product Substances 0.000 description 23
• 239000007787 solid Substances 0.000 description 23
• 239000000706 filtrate Substances 0.000 description 21
• JRZDBBCBIQEJLA-UHFFFAOYSA-N 3,6-dichloro-4-propan-2-ylpyridazine Chemical compound CC(C)C1=CC(Cl)=NN=C1Cl JRZDBBCBIQEJLA-UHFFFAOYSA-N 0.000 description 19
• 229910004373 HOAc Inorganic materials 0.000 description 17
• 239000012043 crude product Substances 0.000 description 17
• 238000004440 column chromatography Methods 0.000 description 16
• 239000003814 drug Substances 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• ACRWOHPZAJEREA-UHFFFAOYSA-N 6-(4-amino-2,6-dichlorophenoxy)-2-methyl-4-propan-2-ylpyridazin-3-one Chemical compound CN1C(=O)C(C(C)C)=CC(OC=2C(=CC(N)=CC=2Cl)Cl)=N1 ACRWOHPZAJEREA-UHFFFAOYSA-N 0.000 description 13
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 13
• 239000012299 nitrogen atmosphere Substances 0.000 description 13
• XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 13
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 13
• 239000003643 water by type Substances 0.000 description 13
• OXAZWPBCFXICCS-UHFFFAOYSA-N 3-[(4-amino-2,6-dichlorophenyl)methyl]-5-propan-2-yl-1h-pyridazin-6-one Chemical compound N1C(=O)C(C(C)C)=CC(CC=2C(=CC(N)=CC=2Cl)Cl)=N1 OXAZWPBCFXICCS-UHFFFAOYSA-N 0.000 description 12
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 12
• 125000004414 alkyl thio group Chemical group 0.000 description 12
• 125000001769 aryl amino group Chemical group 0.000 description 12
• 125000005110 aryl thio group Chemical group 0.000 description 12
• 125000004104 aryloxy group Chemical group 0.000 description 12
• 125000006310 cycloalkyl amino group Chemical group 0.000 description 12
• 125000005366 cycloalkylthio group Chemical group 0.000 description 12
• 125000005241 heteroarylamino group Chemical group 0.000 description 12
• 125000005553 heteroaryloxy group Chemical group 0.000 description 12
• 125000005368 heteroarylthio group Chemical group 0.000 description 12
• 125000005844 heterocyclyloxy group Chemical group 0.000 description 12
• 125000004468 heterocyclylthio group Chemical group 0.000 description 12
• 239000012535 impurity Substances 0.000 description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
• 239000000376 reactant Substances 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 11
• 239000002904 solvent Substances 0.000 description 11
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 10
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 10
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 125000004093 cyano group Chemical group *C#N 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 125000006239 protecting group Chemical group 0.000 description 10
• 238000006467 substitution reaction Methods 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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• IJIULYGLIRUFPE-UHFFFAOYSA-N 3,5-dichloro-4-(6-chloro-5-propan-2-ylpyridazin-3-yl)oxyaniline Chemical compound N1=C(Cl)C(C(C)C)=CC(OC=2C(=CC(N)=CC=2Cl)Cl)=N1 IJIULYGLIRUFPE-UHFFFAOYSA-N 0.000 description 9
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• LGRFSURHDFAFJT-UHFFFAOYSA-N phthalic anhydride Chemical compound C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 9
• GTBHHQSRVAXMMQ-UHFFFAOYSA-N 2-(4-amino-2,6-dichlorophenyl)-2-(6-chloro-5-propan-2-ylpyridazin-3-yl)acetonitrile Chemical compound N1=C(Cl)C(C(C)C)=CC(C(C#N)C=2C(=CC(N)=CC=2Cl)Cl)=N1 GTBHHQSRVAXMMQ-UHFFFAOYSA-N 0.000 description 8
• KFUPGMNNFOGXCW-UHFFFAOYSA-N 2-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyanilino]acetonitrile Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)NCC#N KFUPGMNNFOGXCW-UHFFFAOYSA-N 0.000 description 8
• PFQNEKHHAFIRRV-UHFFFAOYSA-N 3-(4-amino-2,6-dichlorophenoxy)-5-propan-2-yl-1h-pyridazin-6-one Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(N)=CC=2Cl)Cl)=N1 PFQNEKHHAFIRRV-UHFFFAOYSA-N 0.000 description 8
• ILINSDIBSVUTEC-UHFFFAOYSA-N 3-[(4-amino-2,6-dichlorophenyl)methyl]-5-cyclopropyl-1H-pyridazin-6-one Chemical compound NC1=CC(=C(CC=2C=C(C(NN=2)=O)C2CC2)C(=C1)Cl)Cl ILINSDIBSVUTEC-UHFFFAOYSA-N 0.000 description 8
• OISQVGDLLFNCIE-UHFFFAOYSA-N 4-[5-[1-[tert-butyl(dimethyl)silyl]oxypropan-2-yl]-6-chloropyridazin-3-yl]oxy-3,5-dichloroaniline Chemical compound [Si](C)(C)(C(C)(C)C)OCC(C)C=1C=C(N=NC=1Cl)OC1=C(C=C(N)C=C1Cl)Cl OISQVGDLLFNCIE-UHFFFAOYSA-N 0.000 description 8
• KGEXISHTCZHGFT-UHFFFAOYSA-N 4-azaniumyl-2,6-dichlorophenolate Chemical compound NC1=CC(Cl)=C(O)C(Cl)=C1 KGEXISHTCZHGFT-UHFFFAOYSA-N 0.000 description 8
• RPHXCXQDQREHAW-UHFFFAOYSA-N 6-(4-amino-2,6-dichlorophenyl)sulfanyl-2-methyl-4-propan-2-ylpyridazin-3-one Chemical compound CN1C(=O)C(C(C)C)=CC(SC=2C(=CC(N)=CC=2Cl)Cl)=N1 RPHXCXQDQREHAW-UHFFFAOYSA-N 0.000 description 8
• 208000032928 Dyslipidaemia Diseases 0.000 description 8
• 208000017170 Lipid metabolism disease Diseases 0.000 description 8
• JASLSVUTHOQGSW-UHFFFAOYSA-N N-[3,5-dichloro-2-methyl-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]-5-oxo-4H-1,2,4-oxadiazole-3-carboxamide Chemical compound ClC=1C(=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)NC(=O)C1=NOC(N1)=O)C JASLSVUTHOQGSW-UHFFFAOYSA-N 0.000 description 8
• 125000003277 amino group Chemical group 0.000 description 8
• ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 8
• 150000001721 carbon Chemical group 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• LGLZFHKCTJYNCK-UHFFFAOYSA-N o-(2,6-dichloro-4-nitrophenyl) n,n-dimethylcarbamothioate Chemical compound CN(C)C(=S)OC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl LGLZFHKCTJYNCK-UHFFFAOYSA-N 0.000 description 8
• 238000004808 supercritical fluid chromatography Methods 0.000 description 8
• 150000003573 thiols Chemical class 0.000 description 8
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 8
• UQIKMPKXWODKRG-UHFFFAOYSA-N 2-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyphenyl]isoindole-1,3-dione Chemical compound CN1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(C3=CC=CC=C3C2=O)=O)Cl)=N1 UQIKMPKXWODKRG-UHFFFAOYSA-N 0.000 description 7
• NMQHHLWLAVRNJY-UHFFFAOYSA-N 3-[1-[3,5-dichloro-4-(1-methyl-6-oxo-5-propan-2-ylpyridazin-3-yl)oxyanilino]ethyl]-4H-1,2,4-oxadiazol-5-one Chemical compound ClC=1C=C(C=C(C=1OC1=NN(C(C(=C1)C(C)C)=O)C)Cl)NC(C)C1=NOC(N1)=O NMQHHLWLAVRNJY-UHFFFAOYSA-N 0.000 description 7
• CAOSVSPSFQIYQD-UHFFFAOYSA-N 6-(4-amino-2,6-dichloro-3-methylphenoxy)-2-methyl-4-propan-2-ylpyridazin-3-one Chemical compound NC1=C(C(=C(OC=2C=C(C(N(N=2)C)=O)C(C)C)C(=C1)Cl)Cl)C CAOSVSPSFQIYQD-UHFFFAOYSA-N 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
• 208000035150 Hypercholesterolemia Diseases 0.000 description 7
• 208000001145 Metabolic Syndrome Diseases 0.000 description 7
• JFBAKIHKFDLPEU-UHFFFAOYSA-N N-[3,5-dichloro-4-[(5-cyclopropyl-6-oxo-1H-pyridazin-3-yl)oxy]phenyl]-5-oxo-4H-1,2,4-oxadiazole-3-carboxamide Chemical compound ClC=1C=C(C=C(C=1OC1=NNC(C(=C1)C1CC1)=O)Cl)NC(=O)C1=NOC(N1)=O JFBAKIHKFDLPEU-UHFFFAOYSA-N 0.000 description 7
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 7
• 125000002252 acyl group Chemical group 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 208000006575 hypertriglyceridemia Diseases 0.000 description 7
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 7
• KRMVXTWLGCSTHO-UHFFFAOYSA-N 2-(4-amino-2,6-dichlorophenyl)acetonitrile Chemical compound NC1=CC(Cl)=C(CC#N)C(Cl)=C1 KRMVXTWLGCSTHO-UHFFFAOYSA-N 0.000 description 6
• PRIKWTQQRMQQRP-UHFFFAOYSA-N 3,5-dichloro-4-(6-chloro-5-propan-2-ylpyridazin-3-yl)oxybenzonitrile Chemical compound ClC=1C=C(C#N)C=C(C=1OC=1N=NC(=C(C=1)C(C)C)Cl)Cl PRIKWTQQRMQQRP-UHFFFAOYSA-N 0.000 description 6
• MJKIOPPAMRCGJD-UHFFFAOYSA-N 3,5-dichloro-4-[6-chloro-5-[2-(oxan-2-yloxy)propan-2-yl]pyridazin-3-yl]oxyaniline Chemical compound ClC=1C=C(N)C=C(C=1OC=1N=NC(=C(C=1)C(C)(C)OC1OCCCC1)Cl)Cl MJKIOPPAMRCGJD-UHFFFAOYSA-N 0.000 description 6
• QINVTJSYBMDSPK-UHFFFAOYSA-N 5-oxo-2h-1,2,4-oxadiazole-3-carboxylic acid Chemical compound OC(=O)C1=NOC(=O)N1 QINVTJSYBMDSPK-UHFFFAOYSA-N 0.000 description 6
• CBDKXEPTKBUBSW-UHFFFAOYSA-N 6-(4-amino-2,6-dichloro-3-fluorophenoxy)-2-methyl-4-propan-2-ylpyridazin-3-one Chemical compound NC1=C(C(=C(OC=2C=C(C(N(N=2)C)=O)C(C)C)C(=C1)Cl)Cl)F CBDKXEPTKBUBSW-UHFFFAOYSA-N 0.000 description 6
• HJVJWLUMSFAECY-UHFFFAOYSA-N 6-[(4-amino-2,6-dichlorophenyl)methyl]-2-methyl-4-propan-2-ylpyridazin-3-one Chemical compound CN1C(=O)C(C(C)C)=CC(CC=2C(=CC(N)=CC=2Cl)Cl)=N1 HJVJWLUMSFAECY-UHFFFAOYSA-N 0.000 description 6
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 6
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