BR112021010453A2 - Composto, e, composição farmacêutica - Google Patents
Composto, e, composição farmacêutica Download PDFInfo
- Publication number
- BR112021010453A2 BR112021010453A2 BR112021010453-4A BR112021010453A BR112021010453A2 BR 112021010453 A2 BR112021010453 A2 BR 112021010453A2 BR 112021010453 A BR112021010453 A BR 112021010453A BR 112021010453 A2 BR112021010453 A2 BR 112021010453A2
- Authority
- BR
- Brazil
- Prior art keywords
- pyrazol
- mmol
- ethyl
- preparation
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 418
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 168
- -1 -NRcRd Chemical group 0.000 claims description 154
- 125000001424 substituent group Chemical group 0.000 claims description 58
- 102000013691 Interleukin-17 Human genes 0.000 claims description 31
- 108050003558 Interleukin-17 Proteins 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 229910052805 deuterium Inorganic materials 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 17
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 15
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 14
- 125000002883 imidazolyl group Chemical group 0.000 claims description 14
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 12
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 12
- 125000000539 amino acid group Chemical group 0.000 claims description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
- 201000004681 Psoriasis Diseases 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 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 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 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 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 125000006413 ring segment Chemical group 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 6
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 5
- 229910000397 disodium phosphate Inorganic materials 0.000 claims 4
- 235000019800 disodium phosphate Nutrition 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 239000001488 sodium phosphate Substances 0.000 claims 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 3
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims 2
- YAXXTBOSWVLFKN-GIIVHJRKSA-N CC(C)N1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC(O)=C1C1=C(C)NN=C1C)=O)=O Chemical compound CC(C)N1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC(O)=C1C1=C(C)NN=C1C)=O)=O YAXXTBOSWVLFKN-GIIVHJRKSA-N 0.000 claims 1
- IXAOEMKCICGOOH-ADSMNUKGSA-N CC(C)N1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound CC(C)N1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O IXAOEMKCICGOOH-ADSMNUKGSA-N 0.000 claims 1
- CLTKXKOOCSXJOU-LYTHVRBOSA-N CC(CO)N1N=CC=C1C(N[C@@H](C(C1CCC1)C1CCC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound CC(CO)N1N=CC=C1C(N[C@@H](C(C1CCC1)C1CCC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O CLTKXKOOCSXJOU-LYTHVRBOSA-N 0.000 claims 1
- CBGYMFROYVSAIQ-TUXUZCGSSA-N CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CC1)C1CC1)NC(C1=CC=NN1CCC(C(F)(F)F)O)=O)=O Chemical compound CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CC1)C1CC1)NC(C1=CC=NN1CCC(C(F)(F)F)O)=O)=O CBGYMFROYVSAIQ-TUXUZCGSSA-N 0.000 claims 1
- MYWBGJZHKUAMGB-VWLOTQADSA-N CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CC1)C1CC1)NC(C1=CC=NN1CCCO)=O)=O Chemical compound CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CC1)C1CC1)NC(C1=CC=NN1CCCO)=O)=O MYWBGJZHKUAMGB-VWLOTQADSA-N 0.000 claims 1
- AGAMBQBVAANKRZ-MHZLTWQESA-N CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CCC1)C1CCC1)NC(C1=CC=NN1CCCO)=O)=O Chemical compound CC(NN=C1C)=C1C(C=C1)=CC=C1NC([C@H](C(C1CCC1)C1CCC1)NC(C1=CC=NN1CCCO)=O)=O AGAMBQBVAANKRZ-MHZLTWQESA-N 0.000 claims 1
- LNXOEFGFRPXTBS-VWLOTQADSA-N CCCN1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound CCCN1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O LNXOEFGFRPXTBS-VWLOTQADSA-N 0.000 claims 1
- PXIJZVHFBHBXLI-DEOSSOPVSA-N CCN1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound CCN1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O PXIJZVHFBHBXLI-DEOSSOPVSA-N 0.000 claims 1
- AYOYQBYOQVDODV-YFBXQHAESA-N CCN1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound CCN1N=CC=C1C(N[C@@H]([C@H]1CC[C@H](C)CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O AYOYQBYOQVDODV-YFBXQHAESA-N 0.000 claims 1
- DINQHRFCSWADME-SXBQZSJRSA-N C[C@@H](CO)N1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC(F)=C1C1=C(C)NN=C1C)=O)=O Chemical compound C[C@@H](CO)N1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC(F)=C1C1=C(C)NN=C1C)=O)=O DINQHRFCSWADME-SXBQZSJRSA-N 0.000 claims 1
- DLRONPYBUOVQDX-MQNRADLISA-N C[C@@H](CO)N1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O Chemical compound C[C@@H](CO)N1N=CC=C1C(N[C@@H](C(C1CC1)C1CC1)C(NC(C=C1)=CC=C1C1=C(C)NN=C1C)=O)=O DLRONPYBUOVQDX-MQNRADLISA-N 0.000 claims 1
- JDNBJNGGPQVZKJ-SOKVYYICSA-N N-[(2S)-1,1-dicyclopropyl-3-[4-(3,5-diethyl-1H-pyrazol-4-yl)anilino]-3-oxopropan-2-yl]-2-[(2S)-1-hydroxypropan-2-yl]pyrazole-3-carboxamide Chemical compound CCC1=C(C(=NN1)CC)C2=CC=C(C=C2)NC(=O)[C@H](C(C3CC3)C4CC4)NC(=O)C5=CC=NN5[C@@H](C)CO JDNBJNGGPQVZKJ-SOKVYYICSA-N 0.000 claims 1
- NPALCVWCQGHYMW-DEOSSOPVSA-N N-[(2S)-1,1-dicyclopropyl-3-[4-(3,5-dimethyl-1H-pyrazol-4-yl)-3-fluoroanilino]-3-oxopropan-2-yl]-2-ethylpyrazole-3-carboxamide Chemical compound CCN1C(=CC=N1)C(=O)N[C@@H](C(C2CC2)C3CC3)C(=O)NC4=CC(=C(C=C4)C5=C(NN=C5C)C)F NPALCVWCQGHYMW-DEOSSOPVSA-N 0.000 claims 1
- UNZYGPJRUTVUQL-VWLOTQADSA-N N-[(2S)-1,1-dicyclopropyl-3-[4-(3,5-dimethyl-1H-pyrazol-4-yl)-3-hydroxyanilino]-3-oxopropan-2-yl]-2-propan-2-ylpyrazole-3-carboxamide Chemical compound CC1=C(C(=NN1)C)C2=C(C=C(C=C2)NC(=O)[C@H](C(C3CC3)C4CC4)NC(=O)C5=CC=NN5C(C)C)O UNZYGPJRUTVUQL-VWLOTQADSA-N 0.000 claims 1
- CQKVACARDGYEMU-VWLOTQADSA-N N-[(2S)-1,1-dicyclopropyl-3-[4-(3,5-dimethyl-1H-pyrazol-4-yl)anilino]-3-oxopropan-2-yl]-2-propan-2-ylpyrazole-3-carboxamide Chemical group C1(C2=C(C)NN=C2C)=CC=C(NC(=O)[C@@H](NC(=O)C=2N(N=CC=2)C(C)C)C(C2CC2)C2CC2)C=C1 CQKVACARDGYEMU-VWLOTQADSA-N 0.000 claims 1
- KTHYJBOXGYKOKF-MHZLTWQESA-N N-[(2S)-1,1-dicyclopropyl-3-[4-(3-cyclopropyl-5-methyl-1H-pyrazol-4-yl)anilino]-3-oxopropan-2-yl]-2-propan-2-ylpyrazole-3-carboxamide Chemical compound CC1=C(C(=NN1)C2CC2)C3=CC=C(C=C3)NC(=O)[C@H](C(C4CC4)C5CC5)NC(=O)C6=CC=NN6C(C)C KTHYJBOXGYKOKF-MHZLTWQESA-N 0.000 claims 1
- YZXUOOJNNLQURH-VWLOTQADSA-N N-[(2S)-1,1-dicyclopropyl-3-[4-[3-(hydroxymethyl)-5-methyl-1H-pyrazol-4-yl]anilino]-3-oxopropan-2-yl]-2-propan-2-ylpyrazole-3-carboxamide Chemical compound N1(C(C(=O)N[C@@H](C(C2CC2)C2CC2)C(=O)NC2=CC=C(C=3C(=NNC=3CO)C)C=C2)=CC=N1)C(C)C YZXUOOJNNLQURH-VWLOTQADSA-N 0.000 claims 1
- GMTVASUHNIEYNC-UHFFFAOYSA-N N-[1-cyclooctyl-2-[4-(3,5-dimethyl-1H-pyrazol-4-yl)anilino]-2-oxoethyl]-2-(3-hydroxybutyl)pyrazole-3-carboxamide Chemical compound CC1=C(C(=NN1)C)C2=CC=C(C=C2)NC(=O)C(C3CCCCCCC3)NC(=O)C4=CC=NN4CCC(C)O GMTVASUHNIEYNC-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 267
- 239000003814 drug Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000012453 solvate Substances 0.000 abstract description 5
- 150000004677 hydrates Chemical class 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000002500 effect on skin Effects 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 description 411
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 289
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 207
- 238000005160 1H NMR spectroscopy Methods 0.000 description 190
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 175
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 168
- 239000000243 solution Substances 0.000 description 163
- 235000019439 ethyl acetate Nutrition 0.000 description 142
- 239000011541 reaction mixture Substances 0.000 description 128
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 124
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 111
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 98
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 94
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 239000007787 solid Substances 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 62
- 238000006243 chemical reaction Methods 0.000 description 60
- 229910052938 sodium sulfate Inorganic materials 0.000 description 59
- 235000011152 sodium sulphate Nutrition 0.000 description 59
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 57
- 239000002253 acid Substances 0.000 description 55
- 239000007832 Na2SO4 Substances 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- 239000012267 brine Substances 0.000 description 50
- 230000002829 reductive effect Effects 0.000 description 50
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 50
- 239000012044 organic layer Substances 0.000 description 49
- 239000003921 oil Substances 0.000 description 48
- 235000019198 oils Nutrition 0.000 description 48
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 46
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- 239000002904 solvent Substances 0.000 description 45
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
- 238000004440 column chromatography Methods 0.000 description 44
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 35
- 239000006184 cosolvent Substances 0.000 description 35
- 125000004432 carbon atom Chemical group C* 0.000 description 34
- 150000002148 esters Chemical class 0.000 description 34
- 239000012074 organic phase Substances 0.000 description 33
- 125000006239 protecting group Chemical group 0.000 description 33
- 239000000377 silicon dioxide Substances 0.000 description 33
- 150000001412 amines Chemical class 0.000 description 30
- 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 30
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
- 125000006630 butoxycarbonylamino group Chemical group 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000012043 crude product Substances 0.000 description 25
- 239000003480 eluent Substances 0.000 description 25
- 239000008346 aqueous phase Substances 0.000 description 24
- 125000005842 heteroatom Chemical group 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 23
- 235000019341 magnesium sulphate Nutrition 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 229910052786 argon Inorganic materials 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 20
- 229910000027 potassium carbonate Inorganic materials 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 239000010410 layer Substances 0.000 description 18
- 229940002612 prodrug Drugs 0.000 description 18
- 239000000651 prodrug Substances 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
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- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
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- SJHFVQDUQWMQSN-UHFFFAOYSA-N ditert-butyl [3,5-dimethyl-4-(4-nitrophenyl)pyrazol-1-yl]methyl phosphate Chemical compound P(=O)(OC(C)(C)C)(OC(C)(C)C)OCN1N=C(C(=C1C)C1=CC=C(C=C1)[N+](=O)[O-])C SJHFVQDUQWMQSN-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
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- NZGMFVJKRGNMSX-REWPJTCUSA-N ethyl (2S)-2-(benzhydrylideneamino)-2-[(1S)-3-oxocycloheptyl]acetate Chemical compound C1=C(/C(=N/[C@@H]([C@H]2CCCCC(=O)C2)C(=O)OCC)/C2=CC=CC=C2)C=CC=C1 NZGMFVJKRGNMSX-REWPJTCUSA-N 0.000 description 1
- SVTSJMCFIXHFBT-RYUDHWBXSA-N ethyl (2S)-2-[(1S)-3,3-difluorocycloheptyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound CCOC(=O)[C@H]([C@H]1CCCCC(C1)(F)F)NC(=O)OC(C)(C)C SVTSJMCFIXHFBT-RYUDHWBXSA-N 0.000 description 1
- DNTOMSCFVUCJGF-AAEUAGOBSA-N ethyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[(1S)-3-oxocycloheptyl]acetate Chemical compound CCOC(=O)[C@H]([C@H]1CCCCC(=O)C1)NC(=O)OC(C)(C)C DNTOMSCFVUCJGF-AAEUAGOBSA-N 0.000 description 1
- OWELUZGSXGWXER-RYUDHWBXSA-N ethyl (2S)-2-[(7S)-6,6-difluorospiro[2.5]octan-7-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound C(C)(C)(C)OC(=O)N[C@H](C(=O)OCC)[C@H]1C(CCC2(CC2)C1)(F)F OWELUZGSXGWXER-RYUDHWBXSA-N 0.000 description 1
- LPNJODKLXDFVEW-JTQLQIEISA-N ethyl (2S)-2-amino-4-methyl-3-propan-2-ylpentanoate Chemical compound N[C@H](C(=O)OCC)C(C(C)C)C(C)C LPNJODKLXDFVEW-JTQLQIEISA-N 0.000 description 1
- BIUONNZZUCEPQL-ZDUSSCGKSA-N ethyl (2S)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-propan-2-ylpentanoate Chemical compound C(C)(C)(C)OC(=O)N[C@H](C(=O)OCC)C(C(C)C)C(C)C BIUONNZZUCEPQL-ZDUSSCGKSA-N 0.000 description 1
- MIGBNPRGFWDJJX-CPFIQGLUSA-N ethyl (2S)-4-methyl-3-propan-2-yl-2-[(2,4,6-trimethylphenyl)sulfinylamino]pentanoate Chemical compound C(C)(C)C([C@@H](C(=O)OCC)NS(=O)C1=C(C=C(C=C1C)C)C)C(C)C MIGBNPRGFWDJJX-CPFIQGLUSA-N 0.000 description 1
- ASIQQXDTTVRXPV-UHFFFAOYSA-N ethyl 2-(2,2-difluoropropyl)pyrazole-3-carboxylate Chemical compound FC(CN1N=CC=C1C(=O)OCC)(C)F ASIQQXDTTVRXPV-UHFFFAOYSA-N 0.000 description 1
- QNCSWFFFEZQJNV-UHFFFAOYSA-N ethyl 2-(2-methylsulfonylethyl)pyrazole-3-carboxylate Chemical compound CS(=O)(=O)CCN1N=CC=C1C(=O)OCC QNCSWFFFEZQJNV-UHFFFAOYSA-N 0.000 description 1
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- QJAGULDQNROGFD-UHFFFAOYSA-N ethyl 2-(3,3-dimethylcyclopentyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound C(C)(C)(C)OC(=O)NC(C(=O)OCC)C1CC(CC1)(C)C QJAGULDQNROGFD-UHFFFAOYSA-N 0.000 description 1
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- KNNHWNXTFGLIBC-UHFFFAOYSA-N ethyl 2-(4,4,4-trifluoro-3-trimethylsilyloxybutyl)pyrazole-3-carboxylate Chemical compound FC(C(CCN1N=CC=C1C(=O)OCC)O[Si](C)(C)C)(F)F KNNHWNXTFGLIBC-UHFFFAOYSA-N 0.000 description 1
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- BBWOXFDBLHKPOH-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)-2-spiro[2.5]octan-6-ylacetate Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)=NC(C(=O)OCC)C1CCC2(CC2)CC1 BBWOXFDBLHKPOH-UHFFFAOYSA-N 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- JGNHJDIXNUPEFZ-UHFFFAOYSA-N spiro[2.5]octan-6-ol Chemical compound C1CC(O)CCC11CC1 JGNHJDIXNUPEFZ-UHFFFAOYSA-N 0.000 description 1
- PXIGSUWVCSOFMF-UHFFFAOYSA-N spiro[2.5]octan-6-one Chemical compound C1CC(=O)CCC11CC1 PXIGSUWVCSOFMF-UHFFFAOYSA-N 0.000 description 1
- VLTQBOSTFKLOLU-UHFFFAOYSA-N spiro[2.5]octan-6-yl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(C=C1)S(=O)(=O)OC1CCC2(CC2)CC1 VLTQBOSTFKLOLU-UHFFFAOYSA-N 0.000 description 1
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- DYEUBGDGNZEKNS-UHFFFAOYSA-N tert-butyl N-[4-[5-bromo-3-methyl-1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]phenyl]carbamate Chemical compound BrC1=C(C(=NN1COCC[Si](C)(C)C)C)C1=CC=C(C=C1)NC(OC(C)(C)C)=O DYEUBGDGNZEKNS-UHFFFAOYSA-N 0.000 description 1
- SEWQGBHPSNDXJS-UHFFFAOYSA-N tert-butyl N-[4-[5-ethenyl-3-methyl-1-(2-trimethylsilylethoxymethyl)pyrazol-4-yl]phenyl]carbamate Chemical compound CC1=NN(C(=C1C1=CC=C(C=C1)NC(OC(C)(C)C)=O)C=C)COCC[Si](C)(C)C SEWQGBHPSNDXJS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 150000005622 tetraalkylammonium hydroxides Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
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- 125000005208 trialkylammonium group Chemical group 0.000 description 1
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- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A—HUMAN NECESSITIES
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
- C07D233/36—One oxygen atom with hydrocarbon radicals, substituted by nitrogen atoms, attached to ring nitrogen atoms
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/68—Halogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/70—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/96—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/107—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
-
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- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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- 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
- C07D405/14—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 three or more hetero rings
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- 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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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| PCT/EP2019/086239 WO2020127685A1 (en) | 2018-12-19 | 2019-12-19 | Amino-acid anilides as small molecule modulators of il-17 |
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