NZ565494A - Xanthine derivatives as selective HM74A agonists - Google Patents

Info

Publication number

NZ565494A

NZ565494A NZ565494A NZ56549406A NZ565494A NZ 565494 A NZ565494 A NZ 565494A NZ 565494 A NZ565494 A NZ 565494A NZ 56549406 A NZ56549406 A NZ 56549406A NZ 565494 A NZ565494 A NZ 565494A

Authority

NZ

New Zealand

Prior art keywords

chloro

dione

purine

dihydro

butyl

Prior art date

2005-08-10

Links

• Espacenet
• Global Dossier
• Discuss

• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title abstract description 30
• 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 title description 26
• 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 title description 24
• 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title description 8
• 239000000556 agonist Substances 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 287
• 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 27
• 150000003839 salts Chemical class 0.000 claims abstract description 21
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 21
• 125000003118 aryl group Chemical group 0.000 claims abstract description 20
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 14
• 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 14
• 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 13
• 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 12
• 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 12
• 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 12
• 206010019280 Heart failures Diseases 0.000 claims abstract description 11
• 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 11
• 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 11
• 208000008589 Obesity Diseases 0.000 claims abstract description 11
• 235000020824 obesity Nutrition 0.000 claims abstract description 11
• 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 10
• 208000000103 Anorexia Nervosa Diseases 0.000 claims abstract description 10
• 206010070901 Diabetic dyslipidaemia Diseases 0.000 claims abstract description 10
• 208000007536 Thrombosis Diseases 0.000 claims abstract description 10
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 10
• 208000029078 coronary artery disease Diseases 0.000 claims abstract description 10
• 208000006011 Stroke Diseases 0.000 claims abstract description 9
• 208000018262 Peripheral vascular disease Diseases 0.000 claims abstract description 8
• 208000022831 chronic renal failure syndrome Diseases 0.000 claims abstract description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
• 208000020832 chronic kidney disease Diseases 0.000 claims abstract description 7
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 156
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 146
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 124
• 229910052757 nitrogen Inorganic materials 0.000 claims description 72
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
• 239000000460 chlorine Substances 0.000 claims description 43
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 37
• 238000011282 treatment Methods 0.000 claims description 30
• 229960003512 nicotinic acid Drugs 0.000 claims description 19
• 235000001968 nicotinic acid Nutrition 0.000 claims description 19
• 239000011664 nicotinic acid Substances 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 125000002950 monocyclic group Chemical group 0.000 claims description 10
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 7
• 239000013543 active substance Substances 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 150000003536 tetrazoles Chemical class 0.000 claims description 5
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 239000005864 Sulphur Substances 0.000 claims description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
• 229920000080 bile acid sequestrant Polymers 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 229940125753 fibrate Drugs 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000001301 oxygen Substances 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 125000003342 alkenyl group Chemical group 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims description 2
• 239000001257 hydrogen Substances 0.000 claims description 2
• 229910052739 hydrogen Inorganic materials 0.000 claims description 2
• 125000005647 linker group Chemical group 0.000 claims description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
• 208000022531 anorexia Diseases 0.000 claims 1
• 206010061428 decreased appetite Diseases 0.000 claims 1
• 125000001424 substituent group Chemical group 0.000 abstract description 5
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 309
• 239000000203 mixture Substances 0.000 description 270
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 260
• -1 alkeny! Chemical group 0.000 description 162
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 149
• 239000000243 solution Substances 0.000 description 136
• 235000019439 ethyl acetate Nutrition 0.000 description 122
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 116
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 115
• 239000007787 solid Substances 0.000 description 114
• 238000000034 method Methods 0.000 description 111
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 108
• 239000000047 product Substances 0.000 description 104
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 82
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 81
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 78
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
• 238000005160 1H NMR spectroscopy Methods 0.000 description 65
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 63
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
• 229910001868 water Inorganic materials 0.000 description 62
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 55
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 49
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 47
• 239000012044 organic layer Substances 0.000 description 46
• 239000012267 brine Substances 0.000 description 44
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 41
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
• 238000000746 purification Methods 0.000 description 40
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 37
• 238000003756 stirring Methods 0.000 description 35
• 230000008569 process Effects 0.000 description 33
• 239000002585 base Substances 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 30
• 239000000377 silicon dioxide Substances 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 239000012043 crude product Substances 0.000 description 27
• 239000003921 oil Substances 0.000 description 27
• 235000019198 oils Nutrition 0.000 description 27
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 26
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
• FAIAJSOSTNJZCI-UHFFFAOYSA-N purine-2,6-dione Chemical compound O=C1NC(=O)C2=NC=NC2=N1 FAIAJSOSTNJZCI-UHFFFAOYSA-N 0.000 description 24
• 238000002360 preparation method Methods 0.000 description 23
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
• 238000009472 formulation Methods 0.000 description 20
• 239000011541 reaction mixture Substances 0.000 description 20
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 19
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
• 201000010099 disease Diseases 0.000 description 19
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 18
• 239000002904 solvent Substances 0.000 description 17
• 238000001816 cooling Methods 0.000 description 16
• 229940093499 ethyl acetate Drugs 0.000 description 16
• 239000000463 material Substances 0.000 description 15
• 229910000027 potassium carbonate Inorganic materials 0.000 description 15
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 14
• 238000004128 high performance liquid chromatography Methods 0.000 description 14
• 239000012535 impurity Substances 0.000 description 14
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
• 235000011181 potassium carbonates Nutrition 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 210000004027 cell Anatomy 0.000 description 12
• GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 102000005962 receptors Human genes 0.000 description 12
• 108020003175 receptors Proteins 0.000 description 12
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
• 230000029936 alkylation Effects 0.000 description 11
• 238000005804 alkylation reaction Methods 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• 239000007822 coupling agent Substances 0.000 description 11
• 238000010828 elution Methods 0.000 description 11
• 239000000284 extract Substances 0.000 description 11
• 239000000543 intermediate Substances 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 238000010626 work up procedure Methods 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical compound CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 210000004369 blood Anatomy 0.000 description 9
• 239000008280 blood Substances 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 239000000523 sample Substances 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 8
• 206010061218 Inflammation Diseases 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
• 206010012601 diabetes mellitus Diseases 0.000 description 8
• 125000001207 fluorophenyl group Chemical group 0.000 description 8
• 230000004054 inflammatory process Effects 0.000 description 8
• 230000037356 lipid metabolism Effects 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
• 238000000634 powder X-ray diffraction Methods 0.000 description 8
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 8
• 239000012453 solvate Substances 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
• 101001035752 Homo sapiens Hydroxycarboxylic acid receptor 3 Proteins 0.000 description 7
• 102100039356 Hydroxycarboxylic acid receptor 3 Human genes 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 230000009286 beneficial effect Effects 0.000 description 7
• 235000021588 free fatty acids Nutrition 0.000 description 7
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 150000005830 nonesterified fatty acids Chemical class 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• WTUVPERXQXSPFE-UHFFFAOYSA-N 8-chloro-3-pentyl-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCCC)C2=C1N(CC=C)C(Cl)=N2 WTUVPERXQXSPFE-UHFFFAOYSA-N 0.000 description 6
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 6
• 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 6
• 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 6
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• FCCCRBDJBTVFSJ-UHFFFAOYSA-N butanehydrazide Chemical compound CCCC(=O)NN FCCCRBDJBTVFSJ-UHFFFAOYSA-N 0.000 description 6
• 230000000052 comparative effect Effects 0.000 description 6
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
• 229960004132 diethyl ether Drugs 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 239000004615 ingredient Substances 0.000 description 6
• 150000002825 nitriles Chemical class 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 5
• YSRCXLROFNRHLU-UHFFFAOYSA-N 2-hydroxyethanimidamide Chemical compound NC(=N)CO YSRCXLROFNRHLU-UHFFFAOYSA-N 0.000 description 5
• CGNXDNSPHUBQDH-UHFFFAOYSA-N 3-butyl-8-chloro-1-[4-(5-pyridin-2-yl-1,2,4-oxadiazol-3-yl)butyl]-7h-purine-2,6-dione Chemical group O=C1N(CCCC)C=2N=C(Cl)NC=2C(=O)N1CCCCC(N=1)=NOC=1C1=CC=CC=N1 CGNXDNSPHUBQDH-UHFFFAOYSA-N 0.000 description 5
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Chemical group 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 5
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• 229940075420 xanthine Drugs 0.000 description 5
• 229940044613 1-propanol Drugs 0.000 description 4
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 4
• HSCHZTCTGIIVMF-UHFFFAOYSA-N 3-(5-benzyl-1,2,4-oxadiazol-3-yl)propan-1-ol Chemical compound OCCCC1=NOC(CC=2C=CC=CC=2)=N1 HSCHZTCTGIIVMF-UHFFFAOYSA-N 0.000 description 4
• UEHBSOZKEHODBZ-UHFFFAOYSA-N 3-butyl-8-chloro-7-prop-2-enylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCCC)C2=C1N(CC=C)C(Cl)=N2 UEHBSOZKEHODBZ-UHFFFAOYSA-N 0.000 description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 4
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
• RDJQLAINZZVEKX-UHFFFAOYSA-N 8-chloro-7-prop-2-enyl-3-propylpurine-2,6-dione Chemical compound O=C1NC(=O)N(CCC)C2=C1N(CC=C)C(Cl)=N2 RDJQLAINZZVEKX-UHFFFAOYSA-N 0.000 description 4
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