TW202317576A - 作為ｉｌ－１７調節劑之咪唑并三吖𠯤衍生物 - Google Patents

Info

Publication number

TW202317576A

TW202317576A TW111124264A TW111124264A TW202317576A TW 202317576 A TW202317576 A TW 202317576A TW 111124264 A TW111124264 A TW 111124264A TW 111124264 A TW111124264 A TW 111124264A TW 202317576 A TW202317576 A TW 202317576A

Authority

TW

Taiwan

Prior art keywords

methyl

imidazo

triacridine

carbonyl

difluorocyclohexyl

Prior art date

2021-07-01

Links

• Espacenet
• Global Dossier
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• XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 title 1
• 238000011282 treatment Methods 0.000 claims abstract description 32
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 14
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 11
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 10
• 230000002265 prevention Effects 0.000 claims abstract description 6
• -1 acrid-1-yl Chemical group 0.000 claims description 423
• 150000001875 compounds Chemical class 0.000 claims description 320
• 125000001424 substituent group Chemical group 0.000 claims description 171
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 147
• 125000000217 alkyl group Chemical group 0.000 claims description 122
• 229910052739 hydrogen Inorganic materials 0.000 claims description 61
• 239000001257 hydrogen Substances 0.000 claims description 60
• 229910052757 nitrogen Inorganic materials 0.000 claims description 50
• 150000003839 salts Chemical class 0.000 claims description 49
• 125000004432 carbon atom Chemical group C* 0.000 claims description 47
• 229910052731 fluorine Inorganic materials 0.000 claims description 47
• 229920006395 saturated elastomer Polymers 0.000 claims description 45
• 239000011737 fluorine Substances 0.000 claims description 44
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 40
• 108050003558 Interleukin-17 Proteins 0.000 claims description 39
• 102000013691 Interleukin-17 Human genes 0.000 claims description 39
• 125000001153 fluoro group Chemical group F* 0.000 claims description 34
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 30
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 28
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 28
• 150000002431 hydrogen Chemical class 0.000 claims description 28
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
• 125000001072 heteroaryl group Chemical group 0.000 claims description 23
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
• DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
• 125000005842 heteroatom Chemical group 0.000 claims description 19
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 18
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
• 125000002950 monocyclic group Chemical group 0.000 claims description 14
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
• 239000000460 chlorine Substances 0.000 claims description 13
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• 125000004434 sulfur atom Chemical group 0.000 claims description 12
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
• JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 8
• 241000009298 Trigla lyra Species 0.000 claims description 7
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 6
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• FYOWKGSBHOFLLM-UHFFFAOYSA-N 2h-oxadiazole-3-carboxamide Chemical compound NC(=O)N1NOC=C1 FYOWKGSBHOFLLM-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 150000001251 acridines Chemical class 0.000 claims description 3
• 125000004122 cyclic group Chemical group 0.000 claims description 3
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 3
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 6
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 11
• 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 abstract description 3
• 230000003389 potentiating effect Effects 0.000 abstract description 3
• SYLTXFOKMOCILU-UHFFFAOYSA-N imidazo[1,2-b][1,2,4]triazine Chemical class N1=CC=NC2=NC=CN21 SYLTXFOKMOCILU-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 420
• 239000000543 intermediate Substances 0.000 description 304
• 238000000034 method Methods 0.000 description 304
• 239000000203 mixture Substances 0.000 description 226
• 235000019439 ethyl acetate Nutrition 0.000 description 209
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 160
• 239000000243 solution Substances 0.000 description 121
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 114
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 96
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 78
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
• 239000011541 reaction mixture Substances 0.000 description 71
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
• 239000002585 base Substances 0.000 description 67
• 238000000746 purification Methods 0.000 description 67
• 239000007787 solid Substances 0.000 description 65
• 239000012267 brine Substances 0.000 description 60
• 238000003818 flash chromatography Methods 0.000 description 60
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 60
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 54
• 238000004458 analytical method Methods 0.000 description 54
• 239000010410 layer Substances 0.000 description 54
• 239000011734 sodium Substances 0.000 description 53
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 47
• 239000007821 HATU Substances 0.000 description 44
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 44
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
• 239000003643 water by type Substances 0.000 description 42
• 239000012044 organic layer Substances 0.000 description 41
• 239000012071 phase Substances 0.000 description 40
• 239000002904 solvent Substances 0.000 description 39
• 239000000284 extract Substances 0.000 description 37
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 30
• 239000000463 material Substances 0.000 description 29
• 238000004440 column chromatography Methods 0.000 description 28
• 239000006260 foam Substances 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 24
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 24
• 229910052736 halogen Inorganic materials 0.000 description 24
• 230000002829 reductive effect Effects 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 23
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
• 125000004093 cyano group Chemical group *C#N 0.000 description 21
• 235000019253 formic acid Nutrition 0.000 description 21
• 239000012074 organic phase Substances 0.000 description 21
• 239000000725 suspension Substances 0.000 description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 19
• 238000004108 freeze drying Methods 0.000 description 19
• 238000004808 supercritical fluid chromatography Methods 0.000 description 19
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 150000002367 halogens Chemical class 0.000 description 18
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 18
• 239000000377 silicon dioxide Substances 0.000 description 18
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 17
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 17
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
• 239000008346 aqueous phase Substances 0.000 description 16
• 230000008569 process Effects 0.000 description 16
• 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 description 15
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 15
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 14
• 125000003943 azolyl group Chemical group 0.000 description 14
• 125000006001 difluoroethyl group Chemical group 0.000 description 14
• 238000010828 elution Methods 0.000 description 14
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 13
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
• 239000007832 Na2SO4 Substances 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 13
• 229910052794 bromium Inorganic materials 0.000 description 13
• 239000013058 crude material Substances 0.000 description 13
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• 229910052938 sodium sulfate Inorganic materials 0.000 description 13
• 235000011152 sodium sulphate Nutrition 0.000 description 13
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 13
• 206010013774 Dry eye Diseases 0.000 description 12
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 12
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
• 208000003556 Dry Eye Syndromes Diseases 0.000 description 11
• 125000003545 alkoxy group Chemical group 0.000 description 11
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 11
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 11
• 239000003054 catalyst Substances 0.000 description 11
• 230000002209 hydrophobic effect Effects 0.000 description 11
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 11
• 125000004076 pyridyl group Chemical group 0.000 description 11
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 11
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 10
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
• 230000005526 G1 to G0 transition Effects 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 10
• 125000005843 halogen group Chemical group 0.000 description 10
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
• 125000003226 pyrazolyl group Chemical group 0.000 description 10
• 125000001425 triazolyl group Chemical group 0.000 description 10
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 9
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 9
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 9
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 9
• CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 9
• HFOSGECIUSSYGW-UHFFFAOYSA-N 2h-oxadiazole-3-carboxylic acid Chemical compound OC(=O)N1NOC=C1 HFOSGECIUSSYGW-UHFFFAOYSA-N 0.000 description 9
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 9
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 9
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 9
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 9
• 239000010502 orange oil Substances 0.000 description 9
• 125000003566 oxetanyl group Chemical group 0.000 description 9
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
• 229910052723 transition metal Inorganic materials 0.000 description 9
• 150000003624 transition metals Chemical class 0.000 description 9
• 102000004127 Cytokines Human genes 0.000 description 8
• 108090000695 Cytokines Proteins 0.000 description 8
• 125000003277 amino group Chemical group 0.000 description 8
• 229910052799 carbon Inorganic materials 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 150000004292 cyclic ethers Chemical class 0.000 description 8
• 125000002720 diazolyl group Chemical group 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
• 235000019341 magnesium sulphate Nutrition 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 125000003107 substituted aryl group Chemical group 0.000 description 8
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 8
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• 101100096578 Arabidopsis thaliana SQD2 gene Proteins 0.000 description 7
• 108090001005 Interleukin-6 Proteins 0.000 description 7
• 235000019502 Orange oil Nutrition 0.000 description 7
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 7
• 235000011114 ammonium hydroxide Nutrition 0.000 description 7
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
• 230000001575 pathological effect Effects 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
• 229910000029 sodium carbonate Inorganic materials 0.000 description 7
• 238000005406 washing Methods 0.000 description 7
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000009286 beneficial effect Effects 0.000 description 6
• 230000005587 bubbling Effects 0.000 description 6
• 235000011089 carbon dioxide Nutrition 0.000 description 6
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