ES2989387T3 - Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb - Google Patents
Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb Download PDFInfo
- Publication number
- ES2989387T3 ES2989387T3 ES20733688T ES20733688T ES2989387T3 ES 2989387 T3 ES2989387 T3 ES 2989387T3 ES 20733688 T ES20733688 T ES 20733688T ES 20733688 T ES20733688 T ES 20733688T ES 2989387 T3 ES2989387 T3 ES 2989387T3
- Authority
- ES
- Spain
- Prior art keywords
- met
- femlo
- mlo
- hydroxy
- dina
- Prior art date
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 10
- 230000001939 inductive effect Effects 0.000 title description 7
- 108091000080 Phosphotransferase Proteins 0.000 title description 5
- 102000020233 phosphotransferase Human genes 0.000 title description 5
- 150000003384 small molecules Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 237
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 26
- 208000035475 disorder Diseases 0.000 claims abstract description 24
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 6
- 208000008589 Obesity Diseases 0.000 claims abstract description 4
- 206010037575 Pustular psoriasis Diseases 0.000 claims abstract description 4
- 201000011510 cancer Diseases 0.000 claims abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 4
- 208000002557 hidradenitis Diseases 0.000 claims abstract description 4
- 201000007162 hidradenitis suppurativa Diseases 0.000 claims abstract description 4
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 4
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 4
- 235000020824 obesity Nutrition 0.000 claims abstract description 4
- 201000010914 pustulosis of palm and sole Diseases 0.000 claims abstract description 4
- 208000011797 pustulosis palmaris et plantaris Diseases 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 117
- 150000003839 salts Chemical class 0.000 claims description 115
- -1 3-(4-aminopyrido[3,2-d]pyrimidin-6-yl-2-d)phenyl Chemical group 0.000 claims description 63
- 229910052757 nitrogen Inorganic materials 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 102000019148 NF-kappaB-inducing kinase activity proteins Human genes 0.000 claims description 42
- 108040008091 NF-kappaB-inducing kinase activity proteins Proteins 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 18
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 230000001404 mediated effect Effects 0.000 claims description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 8
- 229910052805 deuterium Inorganic materials 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- SYDSHTZOHFOVFO-WRLIODQTSA-N (3S)-3-[2-[3-(2-deuterio-4-imino-1H-pyrido[3,2-d]pyrimidin-6-yl)phenyl]ethynyl]-3-hydroxy-1-methylpyrrolidin-2-one Chemical compound NC=1C2=C(N=C(N=1)[2H])C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O SYDSHTZOHFOVFO-WRLIODQTSA-N 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 201000011152 Pemphigus Diseases 0.000 claims description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 3
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- BMGCLNUWPNEMRQ-NRFANRHFSA-N NC=1C2=C(N=CN=1)CCN(C2)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=CN=1)CCN(C2)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C)=O)O BMGCLNUWPNEMRQ-NRFANRHFSA-N 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 abstract description 4
- 206010025323 Lymphomas Diseases 0.000 abstract description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 abstract description 2
- 230000003466 anti-cipated effect Effects 0.000 abstract description 2
- 208000032839 leukemia Diseases 0.000 abstract description 2
- 230000036210 malignancy Effects 0.000 abstract description 2
- 201000000050 myeloid neoplasm Diseases 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 571
- 239000000203 mixture Substances 0.000 description 384
- 239000007787 solid Substances 0.000 description 320
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 237
- 239000000243 solution Substances 0.000 description 211
- 235000019439 ethyl acetate Nutrition 0.000 description 192
- 238000000132 electrospray ionisation Methods 0.000 description 189
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 173
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 135
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 135
- 238000005160 1H NMR spectroscopy Methods 0.000 description 133
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 130
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 130
- 238000003818 flash chromatography Methods 0.000 description 109
- 239000012044 organic layer Substances 0.000 description 98
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 85
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 80
- 239000012267 brine Substances 0.000 description 79
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 79
- 238000001914 filtration Methods 0.000 description 78
- 239000003208 petroleum Substances 0.000 description 76
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 59
- 229920006395 saturated elastomer Polymers 0.000 description 55
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 49
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
- 235000011152 sodium sulphate Nutrition 0.000 description 42
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 39
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 38
- 239000007832 Na2SO4 Substances 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- 239000000725 suspension Substances 0.000 description 37
- 239000003921 oil Substances 0.000 description 36
- 235000019198 oils Nutrition 0.000 description 36
- 238000003756 stirring Methods 0.000 description 35
- PFCHFHIRKBAQGU-UHFFFAOYSA-N 3-hexanone Chemical compound CCCC(=O)CC PFCHFHIRKBAQGU-UHFFFAOYSA-N 0.000 description 34
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000012298 atmosphere Substances 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 29
- 235000017557 sodium bicarbonate Nutrition 0.000 description 29
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000000284 extract Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000012299 nitrogen atmosphere Substances 0.000 description 23
- 239000012071 phase Substances 0.000 description 22
- 238000000746 purification Methods 0.000 description 21
- 125000001424 substituent group Chemical group 0.000 description 21
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 235000019270 ammonium chloride Nutrition 0.000 description 20
- 229910052799 carbon Inorganic materials 0.000 description 20
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 20
- GKPOMITUDGXOSB-UHFFFAOYSA-N but-3-yn-2-ol Chemical compound CC(O)C#C GKPOMITUDGXOSB-UHFFFAOYSA-N 0.000 description 19
- 125000000217 alkyl group Chemical group 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- 238000000926 separation method Methods 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 15
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 15
- 235000015320 potassium carbonate Nutrition 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000005909 Kieselgur Substances 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 12
- 239000012065 filter cake Substances 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- 241000521257 Hydrops Species 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 206010030113 Oedema Diseases 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910052702 rhenium Inorganic materials 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 235000011089 carbon dioxide Nutrition 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 8
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 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 8
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 125000001188 haloalkyl group Chemical group 0.000 description 7
- 239000012456 homogeneous solution Substances 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 7
- RKJOSOCBDGSTIJ-ZETCQYMHSA-N (3r)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one Chemical compound CN1CC[C@@](O)(C#C)C1=O RKJOSOCBDGSTIJ-ZETCQYMHSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- GKWMWWUBXMYJEU-UHFFFAOYSA-N 3-amino-2-chloropyridine-4-carbaldehyde Chemical compound NC1=C(Cl)N=CC=C1C=O GKWMWWUBXMYJEU-UHFFFAOYSA-N 0.000 description 6
- OCZSHUDRIPCTBS-UHFFFAOYSA-N 3-amino-2-chloropyridine-4-carboxylic acid Chemical compound NC1=C(Cl)N=CC=C1C(O)=O OCZSHUDRIPCTBS-UHFFFAOYSA-N 0.000 description 6
- DTELTOREECFDBC-UHFFFAOYSA-N 3-iodobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(I)=C1 DTELTOREECFDBC-UHFFFAOYSA-N 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
- 241001649081 Dina Species 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 6
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- HSHFNMSHDHAHDN-UHFFFAOYSA-N 2-(3-iodophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(I)=C1 HSHFNMSHDHAHDN-UHFFFAOYSA-N 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 5
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- IRWCCQNHZKTMBC-HXUWFJFHSA-N NC1=NC=NC2=C1N=C(N=C2C)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=NC2=C1N=C(N=C2C)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O IRWCCQNHZKTMBC-HXUWFJFHSA-N 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 5
- VUHVCMJKJLGRJX-UHFFFAOYSA-N tert-butyl n-(2-chloropyridin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN=C1Cl VUHVCMJKJLGRJX-UHFFFAOYSA-N 0.000 description 5
- JJCFOOAPKUJAIV-SSDOTTSWSA-N (2r)-2-(1,3-thiazol-2-yl)but-3-yn-2-ol Chemical compound C#C[C@](O)(C)C1=NC=CS1 JJCFOOAPKUJAIV-SSDOTTSWSA-N 0.000 description 4
- REMKRZLFPLDTKR-UHFFFAOYSA-N (3-trimethylsilylphenyl)boronic acid Chemical compound C[Si](C)(C)C1=CC=CC(B(O)O)=C1 REMKRZLFPLDTKR-UHFFFAOYSA-N 0.000 description 4
- BCMVNFPVKGHFCB-QMMMGPOBSA-N (3r)-3-ethynyl-3-hydroxy-1-methylpiperidin-2-one Chemical compound CN1CCC[C@@](O)(C#C)C1=O BCMVNFPVKGHFCB-QMMMGPOBSA-N 0.000 description 4
- YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- XGQXEWQLZXWKTB-UHFFFAOYSA-N 5-chloro-3-nitro-2H-pyrazolo[4,3-b]pyridine Chemical compound ClC1=CC=C2C(=N1)C(=NN2)[N+](=O)[O-] XGQXEWQLZXWKTB-UHFFFAOYSA-N 0.000 description 4
- FEAABGZUINWQRQ-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)Cl Chemical compound BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)Cl FEAABGZUINWQRQ-UHFFFAOYSA-N 0.000 description 4
- QCFKWOCUWWTVPP-UHFFFAOYSA-N BrC=1C=C2C(=NC=NC2=C(C=1)I)Cl Chemical compound BrC=1C=C2C(=NC=NC2=C(C=1)I)Cl QCFKWOCUWWTVPP-UHFFFAOYSA-N 0.000 description 4
- DEWINFSGUMWZTN-SECBINFHSA-N C(#C)[C@@]1(C(C(CC1)(C)C)=O)O Chemical compound C(#C)[C@@]1(C(C(CC1)(C)C)=O)O DEWINFSGUMWZTN-SECBINFHSA-N 0.000 description 4
- DEWINFSGUMWZTN-VIFPVBQESA-N C(#C)[C@]1(C(C(CC1)(C)C)=O)O Chemical compound C(#C)[C@]1(C(C(CC1)(C)C)=O)O DEWINFSGUMWZTN-VIFPVBQESA-N 0.000 description 4
- CYKRWPBBZNKEFA-QMMMGPOBSA-N CC=1N=CSC=1[C@](C)(C#C)O Chemical compound CC=1N=CSC=1[C@](C)(C#C)O CYKRWPBBZNKEFA-QMMMGPOBSA-N 0.000 description 4
- HYFYTYDEDNPWIO-MRVPVSSYSA-N CC=1SC(=CN=1)[C@@](C)(C#C)O Chemical compound CC=1SC(=CN=1)[C@@](C)(C#C)O HYFYTYDEDNPWIO-MRVPVSSYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- PEJBSKDRMCYDOD-SSDOTTSWSA-N Cc1nnc(o1)[C@](C)(O)C#C Chemical compound Cc1nnc(o1)[C@](C)(O)C#C PEJBSKDRMCYDOD-SSDOTTSWSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 description 4
- QBXPEJGZJONXBO-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2C)N Chemical compound IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2C)N QBXPEJGZJONXBO-UHFFFAOYSA-N 0.000 description 4
- QZEIEVMDXAWCJF-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=NC=C2C=CN=C(C2=C1)N Chemical compound IC=1C=C(C=CC=1)C1=NC=C2C=CN=C(C2=C1)N QZEIEVMDXAWCJF-UHFFFAOYSA-N 0.000 description 4
- AIPSLIQSCWZKEU-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1OC=2N=CN=C(C=2N=1)N Chemical compound IC=1C=C(C=CC=1)C=1OC=2N=CN=C(C=2N=1)N AIPSLIQSCWZKEU-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- FKVSVHKPLBGNQS-HXUWFJFHSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O FKVSVHKPLBGNQS-HXUWFJFHSA-N 0.000 description 4
- FKVSVHKPLBGNQS-FQEVSTJZSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O FKVSVHKPLBGNQS-FQEVSTJZSA-N 0.000 description 4
- ITUONVWLRBFGNX-UHFFFAOYSA-N NC=1C(=NC(=NC=1C)Cl)C#N Chemical compound NC=1C(=NC(=NC=1C)Cl)C#N ITUONVWLRBFGNX-UHFFFAOYSA-N 0.000 description 4
- RLDYBDXGTWEFJZ-NRFANRHFSA-N NC=1C2=C(N=C(N=1)C)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=C(N=1)C)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O RLDYBDXGTWEFJZ-NRFANRHFSA-N 0.000 description 4
- 229910017906 NH3H2O Inorganic materials 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108010025832 RANK Ligand Proteins 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 102100024568 Tumor necrosis factor ligand superfamily member 11 Human genes 0.000 description 4
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000004305 biphenyl Substances 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000024908 graft versus host disease Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-UHFFFAOYSA-M 0.000 description 4
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 239000008279 sol Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 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 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 3
- NNYIMCWMHNKLNZ-UHFFFAOYSA-N (2-methyl-5-oxocyclopenten-1-yl) acetate Chemical compound CC(=O)OC1=C(C)CCC1=O NNYIMCWMHNKLNZ-UHFFFAOYSA-N 0.000 description 3
- RQTIHVVNRGJRJI-MRVPVSSYSA-N (2R)-2-(5-methyl-1,3-thiazol-2-yl)but-3-yn-2-ol Chemical compound CC1=CN=C(S1)[C@@](C)(C#C)O RQTIHVVNRGJRJI-MRVPVSSYSA-N 0.000 description 3
- PEJBSKDRMCYDOD-ZETCQYMHSA-N (2S)-2-(5-methyl-1,3,4-oxadiazol-2-yl)but-3-yn-2-ol Chemical compound Cc1nnc(o1)[C@@](C)(O)C#C PEJBSKDRMCYDOD-ZETCQYMHSA-N 0.000 description 3
- YUGDGZWIUSSLGX-MRVPVSSYSA-N (2r)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol Chemical compound CC1=CC([C@](C)(O)C#C)=NO1 YUGDGZWIUSSLGX-MRVPVSSYSA-N 0.000 description 3
- YUGDGZWIUSSLGX-QMMMGPOBSA-N (2s)-2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol Chemical compound CC1=CC([C@@](C)(O)C#C)=NO1 YUGDGZWIUSSLGX-QMMMGPOBSA-N 0.000 description 3
- QSFUHFRGUWKAHQ-QMMMGPOBSA-N (2s)-2-pyrimidin-2-ylbut-3-yn-2-ol Chemical compound C#C[C@@](O)(C)C1=NC=CC=N1 QSFUHFRGUWKAHQ-QMMMGPOBSA-N 0.000 description 3
- AFSSVCNPDKKSRR-UHFFFAOYSA-N (3-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Br)=C1 AFSSVCNPDKKSRR-UHFFFAOYSA-N 0.000 description 3
- BCMVNFPVKGHFCB-MRVPVSSYSA-N (3S)-3-ethynyl-3-hydroxy-1-methylpiperidin-2-one Chemical compound CN1CCC[C@](O)(C#C)C1=O BCMVNFPVKGHFCB-MRVPVSSYSA-N 0.000 description 3
- BDQGQHQBNPRPPE-UHFFFAOYSA-N 1-prop-2-enylpyrrolidine-2,3-dione Chemical compound C=CCN1CCC(=O)C1=O BDQGQHQBNPRPPE-UHFFFAOYSA-N 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 3
- 239000005631 2,4-Dichlorophenoxyacetic acid Substances 0.000 description 3
- FHCWGLQDAMYXJS-UHFFFAOYSA-N 2-(3-bromophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(Br)=C1 FHCWGLQDAMYXJS-UHFFFAOYSA-N 0.000 description 3
- GRXGLWLGJHGJST-UHFFFAOYSA-N 2-[5-bromo-2-(trifluoromethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(OC1(C)C)c1cc(Br)ccc1OC(F)(F)F GRXGLWLGJHGJST-UHFFFAOYSA-N 0.000 description 3
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 3
- DALVDSOLDDJAMC-UHFFFAOYSA-N 2-hydroxy-5,5-dimethyl-2-(2-trimethylsilylethynyl)cyclopentan-1-one Chemical compound OC1(C(C(CC1)(C)C)=O)C#C[Si](C)(C)C DALVDSOLDDJAMC-UHFFFAOYSA-N 0.000 description 3
- MEWUNWOAHHUXLF-UHFFFAOYSA-N 2-hydroxy-5,5-dimethylcyclopent-2-en-1-one Chemical compound CC1(C)CC=C(O)C1=O MEWUNWOAHHUXLF-UHFFFAOYSA-N 0.000 description 3
- JMKBKDSTWMFOIM-UHFFFAOYSA-N 2-methyl-6-(3-trimethylsilylphenyl)pteridin-4-amine Chemical compound CC1=NC2=NC=C(N=C2C(=N1)N)C1=CC(=CC=C1)[Si](C)(C)C JMKBKDSTWMFOIM-UHFFFAOYSA-N 0.000 description 3
- GJWIHSTXSFMIBJ-UHFFFAOYSA-N 2-methylsulfanyl-7h-pyrido[3,4-d]pyrimidin-8-one Chemical compound C1=CNC(=O)C2=NC(SC)=NC=C21 GJWIHSTXSFMIBJ-UHFFFAOYSA-N 0.000 description 3
- XDNDSAQVXNZKGP-UHFFFAOYSA-N 3-(1h-pyrrol-2-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=CN1 XDNDSAQVXNZKGP-UHFFFAOYSA-N 0.000 description 3
- QWUCBIZSYQTOAO-UHFFFAOYSA-N 3-amino-2-chloropyridine-4-carboxamide Chemical compound NC(=O)C1=CC=NC(Cl)=C1N QWUCBIZSYQTOAO-UHFFFAOYSA-N 0.000 description 3
- LXPPTTYILHQLJM-UHFFFAOYSA-N 3-amino-6-(3-trimethylsilylphenyl)pyrazine-2-carbonitrile Chemical compound NC=1C(=NC(=CN=1)C1=CC(=CC=C1)[Si](C)(C)C)C#N LXPPTTYILHQLJM-UHFFFAOYSA-N 0.000 description 3
- CHPFCHGKXZKMHV-UHFFFAOYSA-N 3-phenylmethoxy-1h-pyridin-2-one Chemical compound O=C1NC=CC=C1OCC1=CC=CC=C1 CHPFCHGKXZKMHV-UHFFFAOYSA-N 0.000 description 3
- FCNJEINFWXOLQY-UHFFFAOYSA-N 4,6-dichloropyrido[3,2-d]pyrimidine Chemical compound N1=CN=C(Cl)C2=NC(Cl)=CC=C21 FCNJEINFWXOLQY-UHFFFAOYSA-N 0.000 description 3
- UJIAFLBUSAICKJ-UHFFFAOYSA-N 4-(trifluoromethyl)-1,3-thiazole-2-carboxylic acid Chemical compound OC(=O)C1=NC(C(F)(F)F)=CS1 UJIAFLBUSAICKJ-UHFFFAOYSA-N 0.000 description 3
- YBAUXEUJXJTKCH-UHFFFAOYSA-N 4-chloro-6-methylsulfanylpyrimido[5,4-d]pyrimidine Chemical compound N1=CN=C(Cl)C2=NC(SC)=NC=C21 YBAUXEUJXJTKCH-UHFFFAOYSA-N 0.000 description 3
- UXYJMWIHDZCOHX-UHFFFAOYSA-N 4-hydroxy-1-methyl-5-oxo-2h-pyrrole-3-carboxylic acid Chemical compound CN1CC(C(O)=O)=C(O)C1=O UXYJMWIHDZCOHX-UHFFFAOYSA-N 0.000 description 3
- GLDGRWAOQMIMPR-UHFFFAOYSA-N 5,5-dimethyl-2-(2-trimethylsilylethynyl)cyclopent-2-en-1-one Chemical compound CC1(CC=C(C1=O)C#C[Si](C)(C)C)C GLDGRWAOQMIMPR-UHFFFAOYSA-N 0.000 description 3
- PWRHKLKFADDKHS-UHFFFAOYSA-N 5,6-diamino-1h-pyrimidin-4-one Chemical compound NC=1NC=NC(=O)C=1N PWRHKLKFADDKHS-UHFFFAOYSA-N 0.000 description 3
- OMPYFDJVSAMSMA-UHFFFAOYSA-N 5-bromo-1h-indazol-3-amine Chemical compound C1=C(Br)C=C2C(N)=NNC2=C1 OMPYFDJVSAMSMA-UHFFFAOYSA-N 0.000 description 3
- LXKTVNFZAFTUNZ-UHFFFAOYSA-N 5-bromo-2-phenylmethoxypyridine Chemical compound N1=CC(Br)=CC=C1OCC1=CC=CC=C1 LXKTVNFZAFTUNZ-UHFFFAOYSA-N 0.000 description 3
- AARPSEAPSXSFKT-UHFFFAOYSA-N 5-bromo-2-phenylmethoxypyridine-4-carboxylic acid Chemical compound OC(=O)c1cc(OCc2ccccc2)ncc1Br AARPSEAPSXSFKT-UHFFFAOYSA-N 0.000 description 3
- CDYVIRSFYCLQTM-UHFFFAOYSA-N 5-iodo-2-methoxybenzoyl chloride Chemical compound COC1=CC=C(I)C=C1C(Cl)=O CDYVIRSFYCLQTM-UHFFFAOYSA-N 0.000 description 3
- XLPDFBUFTAWCIB-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridin-7-ol Chemical compound C1=CN=C2C(O)CCC2=C1 XLPDFBUFTAWCIB-UHFFFAOYSA-N 0.000 description 3
- OBVUPALDLPJGQG-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridin-7-yl acetate Chemical compound C1=CN=C2C(OC(=O)C)CCC2=C1 OBVUPALDLPJGQG-UHFFFAOYSA-N 0.000 description 3
- ZNTOIYUPLXOHAS-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[1,2-a]imidazol-7-ol Chemical compound C1=CN=C2C(O)CCN21 ZNTOIYUPLXOHAS-UHFFFAOYSA-N 0.000 description 3
- GNENAHOTYMCVSR-UHFFFAOYSA-N 6-chloropyrido[3,2-d]pyrimidine-2,4-diamine Chemical compound N1=C(Cl)C=CC2=NC(N)=NC(N)=C21 GNENAHOTYMCVSR-UHFFFAOYSA-N 0.000 description 3
- DZMNECGHHBBVBC-UHFFFAOYSA-N 7-phenylmethoxy-2h-2,6-naphthyridin-1-one Chemical compound C1=C2C(=O)NC=CC2=CN=C1OCC1=CC=CC=C1 DZMNECGHHBBVBC-UHFFFAOYSA-N 0.000 description 3
- KXRCPMCWQWVZNS-UHFFFAOYSA-N 8-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]-6,7-dihydro-5H-quinolin-8-ol Chemical compound CC1(OB(OC1(C)C)C=1C=C(C=CC=1)C#CC1(CCCC=2C=CC=NC1=2)O)C KXRCPMCWQWVZNS-UHFFFAOYSA-N 0.000 description 3
- NDMWXKDCVLUBQV-UHFFFAOYSA-N 8-chloro-2-(3-iodophenyl)-6-methylpyrido[3,4-d]pyrimidine Chemical compound ClC1=NC(=CC2=C1N=C(N=C2)C1=CC(=CC=C1)I)C NDMWXKDCVLUBQV-UHFFFAOYSA-N 0.000 description 3
- QMICGHGYKZQSQO-UHFFFAOYSA-N 8-chloro-2-methylsulfanylpyrido[3,4-d]pyrimidine Chemical compound C1=CN=C(Cl)C2=NC(SC)=NC=C21 QMICGHGYKZQSQO-UHFFFAOYSA-N 0.000 description 3
- NDIKANCSXLZTNB-UHFFFAOYSA-N 8-methyl-1,4-dioxaspiro[4.4]nonan-9-one Chemical compound O=C1C(C)CCC11OCCO1 NDIKANCSXLZTNB-UHFFFAOYSA-N 0.000 description 3
- NBMJDYGAPOGLPY-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)N Chemical compound BrC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)N NBMJDYGAPOGLPY-UHFFFAOYSA-N 0.000 description 3
- HHQCBUHISQOHSB-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C(F)(F)F Chemical compound BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C(F)(F)F HHQCBUHISQOHSB-UHFFFAOYSA-N 0.000 description 3
- GYLZCVBCCWOWEU-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2C)N Chemical compound BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2C)N GYLZCVBCCWOWEU-UHFFFAOYSA-N 0.000 description 3
- YEXHITFETFNQMZ-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC Chemical compound BrC=1C=C(C=CC=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC YEXHITFETFNQMZ-UHFFFAOYSA-N 0.000 description 3
- NQWVAEKRFBFDTG-UHFFFAOYSA-N BrC=1C=C2C(=NC=NC2=C(C=1)I)N Chemical compound BrC=1C=C2C(=NC=NC2=C(C=1)I)N NQWVAEKRFBFDTG-UHFFFAOYSA-N 0.000 description 3
- GAFMQNJCPZJVLE-UHFFFAOYSA-N BrC=1C=C2C(NC=NC2=C(C=1)I)=O Chemical compound BrC=1C=C2C(NC=NC2=C(C=1)I)=O GAFMQNJCPZJVLE-UHFFFAOYSA-N 0.000 description 3
- GQXCAAUDSQBHMJ-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)N)CC(C)C Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)N)CC(C)C GQXCAAUDSQBHMJ-UHFFFAOYSA-N 0.000 description 3
- ZYSFPEQVSOBMKT-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)CN)CC(C)C Chemical compound BrC=1C=CC(=C(C=1)CN)CC(C)C ZYSFPEQVSOBMKT-UHFFFAOYSA-N 0.000 description 3
- RKJOSOCBDGSTIJ-SIFWRFLFSA-N C(#C)[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O Chemical compound C(#C)[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O RKJOSOCBDGSTIJ-SIFWRFLFSA-N 0.000 description 3
- OESHJQBZWYRHFY-SSDOTTSWSA-N C(#C)[C@@]1(C(N(CC1)CC(F)(F)F)=O)O Chemical compound C(#C)[C@@]1(C(N(CC1)CC(F)(F)F)=O)O OESHJQBZWYRHFY-SSDOTTSWSA-N 0.000 description 3
- RKJOSOCBDGSTIJ-HMQROFFESA-N C(#C)[C@]1(C(N(CC1)C([2H])([2H])[2H])=O)O Chemical compound C(#C)[C@]1(C(N(CC1)C([2H])([2H])[2H])=O)O RKJOSOCBDGSTIJ-HMQROFFESA-N 0.000 description 3
- OESHJQBZWYRHFY-ZETCQYMHSA-N C(#C)[C@]1(C(N(CC1)CC(F)(F)F)=O)O Chemical compound C(#C)[C@]1(C(N(CC1)CC(F)(F)F)=O)O OESHJQBZWYRHFY-ZETCQYMHSA-N 0.000 description 3
- GOZOBQYRMACHCA-GKOSEXJESA-N C(C)(C)(C)OC(=O)N(CCC(C(=O)OC)O)C([2H])([2H])[2H] Chemical compound C(C)(C)(C)OC(=O)N(CCC(C(=O)OC)O)C([2H])([2H])[2H] GOZOBQYRMACHCA-GKOSEXJESA-N 0.000 description 3
- RSSBJFBHGUNRFM-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=NC=C2C=CN=C(C2=C1)OC Chemical compound C(C1=CC=CC=C1)OC1=NC=C2C=CN=C(C2=C1)OC RSSBJFBHGUNRFM-UHFFFAOYSA-N 0.000 description 3
- YOOBUASFXVLMAQ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=C(C(=O)N)C(=CN=1)Br Chemical compound C(C1=CC=CC=C1)OC=1C=C(C(=O)N)C(=CN=1)Br YOOBUASFXVLMAQ-UHFFFAOYSA-N 0.000 description 3
- PQGMTFSBUSOVSR-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=C(C=O)C(=CN=1)Br Chemical compound C(C1=CC=CC=C1)OC=1C=C(C=O)C(=CN=1)Br PQGMTFSBUSOVSR-UHFFFAOYSA-N 0.000 description 3
- YWXMVQLLAYIXOO-UHFFFAOYSA-N CC1(C(C2(OCCO2)CC1)=O)C Chemical compound CC1(C(C2(OCCO2)CC1)=O)C YWXMVQLLAYIXOO-UHFFFAOYSA-N 0.000 description 3
- RQTIHVVNRGJRJI-QMMMGPOBSA-N CC1=CN=C(S1)[C@](C)(C#C)O Chemical compound CC1=CN=C(S1)[C@](C)(C#C)O RQTIHVVNRGJRJI-QMMMGPOBSA-N 0.000 description 3
- CYKRWPBBZNKEFA-MRVPVSSYSA-N CC=1N=CSC=1[C@@](C)(C#C)O Chemical compound CC=1N=CSC=1[C@@](C)(C#C)O CYKRWPBBZNKEFA-MRVPVSSYSA-N 0.000 description 3
- 108010029697 CD40 Ligand Proteins 0.000 description 3
- 102100032937 CD40 ligand Human genes 0.000 description 3
- FGITXBBPUQWPPY-QFIPXVFZSA-N CN(C=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C Chemical compound CN(C=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C FGITXBBPUQWPPY-QFIPXVFZSA-N 0.000 description 3
- JKKDQRDZYSKGDY-UHFFFAOYSA-N COC1=C(CNC=2C3=C(N=CN=2)C=NC(=N3)SC)C=CC(=C1)OC Chemical compound COC1=C(CNC=2C3=C(N=CN=2)C=NC(=N3)SC)C=CC(=C1)OC JKKDQRDZYSKGDY-UHFFFAOYSA-N 0.000 description 3
- WRRFAZMJIHHVNF-UHFFFAOYSA-N COC1=C2C=C(N=CC2=CC=N1)C=1C=C(N)C=CC=1 Chemical compound COC1=C2C=C(N=CC2=CC=N1)C=1C=C(N)C=CC=1 WRRFAZMJIHHVNF-UHFFFAOYSA-N 0.000 description 3
- DJOAHSBLGHBESL-UHFFFAOYSA-N COC1=C2C=C(N=CC2=CC=N1)O Chemical compound COC1=C2C=C(N=CC2=CC=N1)O DJOAHSBLGHBESL-UHFFFAOYSA-N 0.000 description 3
- KIFUIRGTMICPMO-UHFFFAOYSA-N ClC1=CC=C2C(=N1)C(=NN2C)[N+](=O)[O-] Chemical compound ClC1=CC=C2C(=N1)C(=NN2C)[N+](=O)[O-] KIFUIRGTMICPMO-UHFFFAOYSA-N 0.000 description 3
- OTMZQKJVEDAUSK-UHFFFAOYSA-N ClC1=NC=C(C(=C1NC(OC(C)(C)C)=O)C=O)C Chemical compound ClC1=NC=C(C(=C1NC(OC(C)(C)C)=O)C=O)C OTMZQKJVEDAUSK-UHFFFAOYSA-N 0.000 description 3
- OGHKVQVGPPQCCO-UHFFFAOYSA-N ClC1=NC=CC2=C1N=C(NC2=O)C1=CC(=CC=C1)I Chemical compound ClC1=NC=CC2=C1N=C(NC2=O)C1=CC(=CC=C1)I OGHKVQVGPPQCCO-UHFFFAOYSA-N 0.000 description 3
- MGLVOVWEZMSDIN-UHFFFAOYSA-N ClC1=NC=CC2=CN=C(C=C12)C1=CC(=CC=C1)I Chemical compound ClC1=NC=CC2=CN=C(C=C12)C1=CC(=CC=C1)I MGLVOVWEZMSDIN-UHFFFAOYSA-N 0.000 description 3
- HQDGYMAOBVXEEU-UHFFFAOYSA-N ClC=1C2=C(N=CN=1)CCN(C2)C1=CC(=CC=C1)I Chemical compound ClC=1C2=C(N=CN=1)CCN(C2)C1=CC(=CC=C1)I HQDGYMAOBVXEEU-UHFFFAOYSA-N 0.000 description 3
- JVZMKRNTVCJSGB-UHFFFAOYSA-N ClC=1N=CC=2N=C(NC(C=2N=1)=O)C Chemical compound ClC=1N=CC=2N=C(NC(C=2N=1)=O)C JVZMKRNTVCJSGB-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
- ZRHIWSGAMBUDGD-ZETCQYMHSA-N FC(C=1N=C(SC=1)[C@](C)(C#C)O)(F)F Chemical compound FC(C=1N=C(SC=1)[C@](C)(C#C)O)(F)F ZRHIWSGAMBUDGD-ZETCQYMHSA-N 0.000 description 3
- LWHQAKJXTGSQGK-UHFFFAOYSA-N FC(S(=O)(=O)OC=1N=CC2=CC=NC(=C2C=1)OC)(F)F Chemical compound FC(S(=O)(=O)OC=1N=CC2=CC=NC(=C2C=1)OC)(F)F LWHQAKJXTGSQGK-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 3
- HTCHNNXPEPDXEH-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC2=C(N=CN=C2N)C(=N1)C Chemical compound IC=1C=C(C=CC=1)C1=CC2=C(N=CN=C2N)C(=N1)C HTCHNNXPEPDXEH-UHFFFAOYSA-N 0.000 description 3
- OTCUWFHUZVPPQK-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2C)[N+](=O)[O-] Chemical compound IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2C)[N+](=O)[O-] OTCUWFHUZVPPQK-UHFFFAOYSA-N 0.000 description 3
- YOLANMWJBKLGOX-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=NC=C2C=CN=C(C2=C1)OC Chemical compound IC=1C=C(C=CC=1)C1=NC=C2C=CN=C(C2=C1)OC YOLANMWJBKLGOX-UHFFFAOYSA-N 0.000 description 3
- QETMKZUMDWMJSL-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1C=C2C(=NNC2=CC=1)N Chemical compound IC=1C=C(C=CC=1)C=1C=C2C(=NNC2=CC=1)N QETMKZUMDWMJSL-UHFFFAOYSA-N 0.000 description 3
- AHDXDQFXEYEJKC-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=C(C(=C(C(=O)OCC)C=1)[N+](=O)[O-])C Chemical compound IC=1C=C(C=CC=1)C=1N=C(C(=C(C(=O)OCC)C=1)[N+](=O)[O-])C AHDXDQFXEYEJKC-UHFFFAOYSA-N 0.000 description 3
- KOQIOWSFYNAIKL-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=C2C(=NC(=NC2=NC=1)C)N Chemical compound IC=1C=C(C=CC=1)C=1N=C2C(=NC(=NC2=NC=1)C)N KOQIOWSFYNAIKL-UHFFFAOYSA-N 0.000 description 3
- ZBDWUKNFMBOVKN-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC(=C2)C)N Chemical compound IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC(=C2)C)N ZBDWUKNFMBOVKN-UHFFFAOYSA-N 0.000 description 3
- SCTWMJNZYXSARC-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1NC(C2=C(N=1)C(=NC=C2)OC)=O Chemical compound IC=1C=C(C=CC=1)C=1NC(C2=C(N=1)C(=NC=C2)OC)=O SCTWMJNZYXSARC-UHFFFAOYSA-N 0.000 description 3
- KSGRPSJXNZEURD-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1SC2=C(C=NC=C2)N=1 Chemical compound IC=1C=C(C=CC=1)C=1SC2=C(C=NC=C2)N=1 KSGRPSJXNZEURD-UHFFFAOYSA-N 0.000 description 3
- JWBNZFVTUHSZHK-UHFFFAOYSA-N IC=1C=C(C=CC=1)N(CCC(=O)OC)CCC(=O)OC Chemical compound IC=1C=C(C=CC=1)N(CCC(=O)OC)CCC(=O)OC JWBNZFVTUHSZHK-UHFFFAOYSA-N 0.000 description 3
- AJELWXNJOKXZRB-UHFFFAOYSA-N IC=1C=C(C=CC=1)N1CC(C(CC1)=O)C(=O)OC Chemical compound IC=1C=C(C=CC=1)N1CC(C(CC1)=O)C(=O)OC AJELWXNJOKXZRB-UHFFFAOYSA-N 0.000 description 3
- JZLRNWGASWWBPF-UHFFFAOYSA-N IC=1C=C(C=CC=1)N1CC2=C(N=CN=C2N)CC1 Chemical compound IC=1C=C(C=CC=1)N1CC2=C(N=CN=C2N)CC1 JZLRNWGASWWBPF-UHFFFAOYSA-N 0.000 description 3
- JLTWFUOYFBODCO-UHFFFAOYSA-N IC=1C=C(C=CC=1)N1CC2=C(N=CN=C2O)CC1 Chemical compound IC=1C=C(C=CC=1)N1CC2=C(N=CN=C2O)CC1 JLTWFUOYFBODCO-UHFFFAOYSA-N 0.000 description 3
- HOXNRLOUAXMYDN-UHFFFAOYSA-N IC=1C=CC(=C(C=1)C=1SC=2N=CN=C(C=2N=1)N)C Chemical compound IC=1C=CC(=C(C=1)C=1SC=2N=CN=C(C=2N=1)N)C HOXNRLOUAXMYDN-UHFFFAOYSA-N 0.000 description 3
- SKNZEDGVOFUAAD-UHFFFAOYSA-N IC=1C=CC(=C(C=1)C=1SC=2N=CN=C(C=2N=1)N)OC Chemical compound IC=1C=CC(=C(C=1)C=1SC=2N=CN=C(C=2N=1)N)OC SKNZEDGVOFUAAD-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- HWGBHCRJGXAGEU-UHFFFAOYSA-N Methylthiouracil Chemical compound CC1=CC(=O)NC(=S)N1 HWGBHCRJGXAGEU-UHFFFAOYSA-N 0.000 description 3
- RHHQRTMJAABQTD-UHFFFAOYSA-N NC1=C(C(=O)OCC)C=C(N=C1C)C1=CC(=CC=C1)I Chemical compound NC1=C(C(=O)OCC)C=C(N=C1C)C1=CC(=CC=C1)I RHHQRTMJAABQTD-UHFFFAOYSA-N 0.000 description 3
- ZTNRYRULKQERFS-UHFFFAOYSA-N NC1=NC=NC2=C(C=C(C=C12)Br)C#N Chemical compound NC1=NC=NC2=C(C=C(C=C12)Br)C#N ZTNRYRULKQERFS-UHFFFAOYSA-N 0.000 description 3
- IRWCCQNHZKTMBC-FQEVSTJZSA-N NC1=NC=NC2=C1N=C(N=C2C)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=NC2=C1N=C(N=C2C)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O IRWCCQNHZKTMBC-FQEVSTJZSA-N 0.000 description 3
- OQJKWIJXNLPIKT-UHFFFAOYSA-N NC1=NN(C2=CC=C(C=C12)C1=CC(=CC=C1)I)C(=O)OC(C)(C)C Chemical compound NC1=NN(C2=CC=C(C=C12)C1=CC(=CC=C1)I)C(=O)OC(C)(C)C OQJKWIJXNLPIKT-UHFFFAOYSA-N 0.000 description 3
- RLDYBDXGTWEFJZ-OAQYLSRUSA-N NC=1C2=C(N=C(N=1)C)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=C(N=1)C)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O RLDYBDXGTWEFJZ-OAQYLSRUSA-N 0.000 description 3
- CXTMHGLFUDUJLE-IBGZPJMESA-N NC=1C2=C(N=CN=1)SC(=N2)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=CN=1)SC(=N2)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C)=O)O CXTMHGLFUDUJLE-IBGZPJMESA-N 0.000 description 3
- USNXWCSFADUIBY-UHFFFAOYSA-N NC=1N=CNC(C=1NC(C1=CC(=CC=C1)I)=O)=O Chemical compound NC=1N=CNC(C=1NC(C1=CC(=CC=C1)I)=O)=O USNXWCSFADUIBY-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229910019213 POCl3 Inorganic materials 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000010210 aluminium Nutrition 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 3
- INQFIHXHEMNAHH-UHFFFAOYSA-N ethyl 3-(prop-2-enylamino)propanoate Chemical compound CCOC(=O)CCNCC=C INQFIHXHEMNAHH-UHFFFAOYSA-N 0.000 description 3
- PSTFYCCCZHOTHW-UHFFFAOYSA-N ethyl 4-(trifluoromethyl)-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC(C(F)(F)F)=CS1 PSTFYCCCZHOTHW-UHFFFAOYSA-N 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 3
- NHLKVGYPYLXMBV-UHFFFAOYSA-N methyl 1-methyl-2-oxopyrrolidine-3-carboxylate Chemical compound COC(=O)C1CCN(C)C1=O NHLKVGYPYLXMBV-UHFFFAOYSA-N 0.000 description 3
- JWQXIVXGQGOFRB-UKDQJQFQSA-N methyl 2-[tert-butyl(dimethyl)silyl]oxy-4-[(2-methylpropan-2-yl)oxycarbonyl-(trideuteriomethyl)amino]butanoate Chemical compound C(C)(C)(C)OC(=O)N(CCC(C(=O)OC)O[Si](C)(C)C(C)(C)C)C([2H])([2H])[2H] JWQXIVXGQGOFRB-UKDQJQFQSA-N 0.000 description 3
- LXNYTHFAONPXKP-UHFFFAOYSA-N methyl 2-[tert-butyl(dimethyl)silyl]oxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate Chemical compound COC(=O)C(CCNC(=O)OC(C)(C)C)O[Si](C)(C)C(C)(C)C LXNYTHFAONPXKP-UHFFFAOYSA-N 0.000 description 3
- RVTIPPUCNSLRLU-UHFFFAOYSA-N methyl 2-amino-5-bromo-3-methoxybenzoate Chemical compound COC(=O)C1=CC(Br)=CC(OC)=C1N RVTIPPUCNSLRLU-UHFFFAOYSA-N 0.000 description 3
- CXHVARPHUYSNFS-UHFFFAOYSA-N methyl 3-amino-6-chloro-4-methylpyridine-2-carboxylate Chemical compound C1(=CC(=C(C(=N1)C(=O)OC)N)C)Cl CXHVARPHUYSNFS-UHFFFAOYSA-N 0.000 description 3
- 230000008779 noncanonical pathway Effects 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- QFCIMQXNZKRUPC-UHFFFAOYSA-N tert-butyl 3-amino-5-(3-trimethylsilylphenyl)indazole-1-carboxylate Chemical compound NC1=NN(C2=CC=C(C=C12)C1=CC(=CC=C1)[Si](C)(C)C)C(=O)OC(C)(C)C QFCIMQXNZKRUPC-UHFFFAOYSA-N 0.000 description 3
- CFFJDRPLGNKXCR-UHFFFAOYSA-N tert-butyl 3-amino-5-bromoindazole-1-carboxylate Chemical compound BrC1=CC=C2N(C(=O)OC(C)(C)C)N=C(N)C2=C1 CFFJDRPLGNKXCR-UHFFFAOYSA-N 0.000 description 3
- DXOXSLQEUOMVTJ-UHFFFAOYSA-N tert-butyl n-(2-chloro-4-formylpyridin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=C(Cl)N=CC=C1C=O DXOXSLQEUOMVTJ-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- HVXOQJVTKYYNTE-UHFFFAOYSA-N trimethyl-[3-(1-methyl-3-nitropyrazolo[4,3-b]pyridin-5-yl)phenyl]silane Chemical compound CN1N=C(C2=NC(=CC=C21)C1=CC(=CC=C1)[Si](C)(C)C)[N+](=O)[O-] HVXOQJVTKYYNTE-UHFFFAOYSA-N 0.000 description 3
- NPZRXQRSNDOPOT-UHFFFAOYSA-N trimethyl-[3-(3-nitro-2H-pyrazolo[4,3-b]pyridin-5-yl)phenyl]silane Chemical compound [N+](=O)([O-])C1=NNC=2C1=NC(=CC=2)C1=CC(=CC=C1)[Si](C)(C)C NPZRXQRSNDOPOT-UHFFFAOYSA-N 0.000 description 3
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 3
- 235000019798 tripotassium phosphate Nutrition 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- IWOPDHMRPATBIB-MRVPVSSYSA-N (2R)-2-pyrazin-2-ylbut-3-yn-2-ol Chemical compound C[C@@](O)(C#C)c1cnccn1 IWOPDHMRPATBIB-MRVPVSSYSA-N 0.000 description 2
- YCCRSQHGHNGFTN-FQEVSTJZSA-N (2S)-2-(5-methyl-1,3-thiazol-2-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC1=CN=C(S1)[C@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O YCCRSQHGHNGFTN-FQEVSTJZSA-N 0.000 description 2
- IWOPDHMRPATBIB-QMMMGPOBSA-N (2S)-2-pyrazin-2-ylbut-3-yn-2-ol Chemical compound C[C@](O)(C#C)c1cnccn1 IWOPDHMRPATBIB-QMMMGPOBSA-N 0.000 description 2
- SNKQUAATTWNZCV-SECBINFHSA-N (2r)-2-pyridin-2-ylbut-3-yn-2-ol Chemical compound C#C[C@](O)(C)C1=CC=CC=N1 SNKQUAATTWNZCV-SECBINFHSA-N 0.000 description 2
- QSFUHFRGUWKAHQ-MRVPVSSYSA-N (2r)-2-pyrimidin-2-ylbut-3-yn-2-ol Chemical compound C#C[C@](O)(C)C1=NC=CC=N1 QSFUHFRGUWKAHQ-MRVPVSSYSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- JJCFOOAPKUJAIV-ZETCQYMHSA-N (2s)-2-(1,3-thiazol-2-yl)but-3-yn-2-ol Chemical compound C#C[C@@](O)(C)C1=NC=CS1 JJCFOOAPKUJAIV-ZETCQYMHSA-N 0.000 description 2
- SNKQUAATTWNZCV-VIFPVBQESA-N (2s)-2-pyridin-2-ylbut-3-yn-2-ol Chemical compound C#C[C@@](O)(C)C1=CC=CC=N1 SNKQUAATTWNZCV-VIFPVBQESA-N 0.000 description 2
- GYKHKBSIFRQQOX-TUXZPMJESA-N (3R)-3-[2-[3-(2-deuterio-4-imino-1H-pyrido[3,2-d]pyrimidin-6-yl)-4-(trifluoromethoxy)phenyl]ethynyl]-3-hydroxy-1-methylpyrrolidin-2-one Chemical compound NC=1C2=C(N=C(N=1)[2H])C=CC(=N2)C=1C=C(C=CC=1OC(F)(F)F)C#C[C@]1(C(N(CC1)C)=O)O GYKHKBSIFRQQOX-TUXZPMJESA-N 0.000 description 2
- SYDSHTZOHFOVFO-VXQWRZFRSA-N (3R)-3-[2-[3-(2-deuterio-4-imino-1H-pyrido[3,2-d]pyrimidin-6-yl)phenyl]ethynyl]-3-hydroxy-1-methylpyrrolidin-2-one Chemical compound NC=1C2=C(N=C(N=1)[2H])C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O SYDSHTZOHFOVFO-VXQWRZFRSA-N 0.000 description 2
- VQMHVJCELLJDGW-IBGZPJMESA-N (3R)-3-hydroxy-1-methyl-3-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethoxy)phenyl]ethynyl]pyrrolidin-2-one Chemical compound O[C@@]1(C(N(CC1)C)=O)C#CC1=CC(=C(C=C1)OC(F)(F)F)B1OC(C(O1)(C)C)(C)C VQMHVJCELLJDGW-IBGZPJMESA-N 0.000 description 2
- GUPWFVIZCPKTCR-IBGZPJMESA-N (3R)-3-hydroxy-1-methyl-3-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one Chemical compound C1=C(B2OC(C(C)(C)O2)(C)C)C=C(C#C[C@@]2(CCN(C2=O)C)O)C=C1 GUPWFVIZCPKTCR-IBGZPJMESA-N 0.000 description 2
- WINJEFAMOCHYTR-FQEVSTJZSA-N (3R)-3-hydroxy-3-[2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]-1-methylpyrrolidin-2-one Chemical compound O[C@@]1(C(N(CC1)C)=O)C#CC1=CC(=C(C=C1)OC)B1OC(C(O1)(C)C)(C)C WINJEFAMOCHYTR-FQEVSTJZSA-N 0.000 description 2
- GUPWFVIZCPKTCR-LJQANCHMSA-N (3S)-3-hydroxy-1-methyl-3-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one Chemical compound O[C@]1(C(N(CC1)C)=O)C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C GUPWFVIZCPKTCR-LJQANCHMSA-N 0.000 description 2
- QOZFXELTNKMOQP-UHFFFAOYSA-N (5-bromo-2-methylphenyl)boronic acid Chemical compound CC1=CC=C(Br)C=C1B(O)O QOZFXELTNKMOQP-UHFFFAOYSA-N 0.000 description 2
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- ANUKYNIYGCGGNK-UHFFFAOYSA-N 1-(2-methyl-1,3-thiazol-5-yl)ethanone Chemical compound CC(=O)C1=CN=C(C)S1 ANUKYNIYGCGGNK-UHFFFAOYSA-N 0.000 description 2
- ILNWFHDCOPCVDZ-UHFFFAOYSA-N 1-(3-amino-2-chloropyridin-4-yl)ethanone Chemical compound CC(=O)C1=CC=NC(Cl)=C1N ILNWFHDCOPCVDZ-UHFFFAOYSA-N 0.000 description 2
- QPUIPSFYQGKAFL-UHFFFAOYSA-N 1-(4-methyl-1,3-thiazol-2-yl)ethanone Chemical compound CC(=O)C1=NC(C)=CS1 QPUIPSFYQGKAFL-UHFFFAOYSA-N 0.000 description 2
- JCRXSOIVLXSHTN-UHFFFAOYSA-N 1-(5-methyl-1,3,4-oxadiazol-2-yl)ethanone Chemical compound CC(=O)C1=NN=C(C)O1 JCRXSOIVLXSHTN-UHFFFAOYSA-N 0.000 description 2
- ZGOBPVBSAXXNES-UHFFFAOYSA-N 1-(5-methyl-1,3-thiazol-2-yl)ethanone Chemical compound CC(=O)C1=NC=C(C)S1 ZGOBPVBSAXXNES-UHFFFAOYSA-N 0.000 description 2
- NNDFUMFEKPCADK-UHFFFAOYSA-N 1-methylpiperidine-2,3-dione Chemical compound CN1CCCC(=O)C1=O NNDFUMFEKPCADK-UHFFFAOYSA-N 0.000 description 2
- DHFODCCTNFXCCQ-UHFFFAOYSA-N 1-methylpyrrolidine-2,3-dione Chemical compound CN1CCC(=O)C1=O DHFODCCTNFXCCQ-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BSLCBYOXMDACSD-UHFFFAOYSA-N 1-oxido-6,7-dihydro-5h-cyclopenta[b]pyridin-1-ium Chemical compound [O-][N+]1=CC=CC2=C1CCC2 BSLCBYOXMDACSD-UHFFFAOYSA-N 0.000 description 2
- SPZUXKZZYDALEY-UHFFFAOYSA-N 1-pyrimidin-2-ylethanone Chemical compound CC(=O)C1=NC=CC=N1 SPZUXKZZYDALEY-UHFFFAOYSA-N 0.000 description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
- UQFHLJKWYIJISA-UHFFFAOYSA-N 2,6-dimethyl-1h-pyrimidin-4-one Chemical compound CC1=CC(O)=NC(C)=N1 UQFHLJKWYIJISA-UHFFFAOYSA-N 0.000 description 2
- PYHGMRPBEQFDEC-UHFFFAOYSA-N 2-(2-hydroxyethyl)benzonitrile Chemical compound OCCC1=CC=CC=C1C#N PYHGMRPBEQFDEC-UHFFFAOYSA-N 0.000 description 2
- PEJBSKDRMCYDOD-UHFFFAOYSA-N 2-(5-methyl-1,3,4-oxadiazol-2-yl)but-3-yn-2-ol Chemical compound CC1=NN=C(C(C)(O)C#C)O1 PEJBSKDRMCYDOD-UHFFFAOYSA-N 0.000 description 2
- DBZAKQWXICEWNW-UHFFFAOYSA-N 2-acetylpyrazine Chemical compound CC(=O)C1=CN=CC=N1 DBZAKQWXICEWNW-UHFFFAOYSA-N 0.000 description 2
- CPPQOSMKJDPRID-UHFFFAOYSA-M 2-carboxy-6-methylphenolate;copper(1+) Chemical compound [Cu+].CC1=CC=CC(C([O-])=O)=C1O CPPQOSMKJDPRID-UHFFFAOYSA-M 0.000 description 2
- HNPYFNFNUQMCFP-VMNATFBRSA-N 2-chloro-6-deuterio-4-methylpyrimido[5,4-d]pyrimidin-8-amine Chemical compound ClC=1N=C(C=2N=C(N=C(C=2N=1)N)[2H])C HNPYFNFNUQMCFP-VMNATFBRSA-N 0.000 description 2
- QCOKYYIIWNBHRM-UHFFFAOYSA-N 2-chloro-7h-1,7-naphthyridin-8-one Chemical compound C1=CNC(=O)C2=NC(Cl)=CC=C21 QCOKYYIIWNBHRM-UHFFFAOYSA-N 0.000 description 2
- HAIYEFMGUXOXIY-UHFFFAOYSA-N 2-fluoroethanimidamide Chemical compound NC(=N)CF HAIYEFMGUXOXIY-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- CFAKWWQIUFSQFU-UHFFFAOYSA-N 2-hydroxy-3-methylcyclopent-2-en-1-one Chemical compound CC1=C(O)C(=O)CC1 CFAKWWQIUFSQFU-UHFFFAOYSA-N 0.000 description 2
- POASMXSJVKADPM-UHFFFAOYSA-N 2-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCCC(O)C(O)=O POASMXSJVKADPM-UHFFFAOYSA-N 0.000 description 2
- DCOMNCHHWKSAJA-UHFFFAOYSA-N 2-methyl-6-(3-trimethylsilylphenyl)pyrido[3,2-d]pyrimidin-4-amine Chemical compound CC=1N=C(C2=C(N=1)C=CC(=N2)C1=CC(=CC=C1)[Si](C)(C)C)N DCOMNCHHWKSAJA-UHFFFAOYSA-N 0.000 description 2
- MZQLLIPPUDIMSI-UHFFFAOYSA-N 2-methylsulfanylpyrido[3,4-d]pyrimidin-8-amine Chemical compound C1=CN=C(N)C2=NC(SC)=NC=C21 MZQLLIPPUDIMSI-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- LFYNAOKCQMWRQM-UHFFFAOYSA-N 3-hydroxy-1-methyl-3-(2-trimethylsilylethynyl)piperidin-2-one Chemical compound OC1(C(N(CCC1)C)=O)C#C[Si](C)(C)C LFYNAOKCQMWRQM-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- ZGWGSEUMABQEMD-UHFFFAOYSA-N 4-methyl-1,3-thiazole-5-carboxylic acid Chemical compound CC=1N=CSC=1C(O)=O ZGWGSEUMABQEMD-UHFFFAOYSA-N 0.000 description 2
- ZULJQRMXUOTWBU-UHFFFAOYSA-N 5,6-dihydrocyclopenta[b]pyridin-7-one Chemical compound C1=CN=C2C(=O)CCC2=C1 ZULJQRMXUOTWBU-UHFFFAOYSA-N 0.000 description 2
- JXQCJYNMPFHDED-UHFFFAOYSA-N 5,6-dihydropyrrolo[1,2-a]imidazol-7-one Chemical compound C1=CN=C2C(=O)CCN21 JXQCJYNMPFHDED-UHFFFAOYSA-N 0.000 description 2
- LNXBMWBKHDYMAY-UHFFFAOYSA-N 5-bromo-2-(2-methylpropyl)benzonitrile Chemical compound CC(C)CC1=CC=C(Br)C=C1C#N LNXBMWBKHDYMAY-UHFFFAOYSA-N 0.000 description 2
- RQXUDXAAXGXEEU-UHFFFAOYSA-N 6-bromopyrido[2,3-d]pyrimidin-4-amine Chemical compound C1=C(Br)C=C2C(N)=NC=NC2=N1 RQXUDXAAXGXEEU-UHFFFAOYSA-N 0.000 description 2
- PLEZEDWYEZXICN-UHFFFAOYSA-N 6-bromopyrido[3,2-d]pyrimidin-4-amine Chemical compound Nc1ncnc2ccc(Br)nc12 PLEZEDWYEZXICN-UHFFFAOYSA-N 0.000 description 2
- NPNSDEDMKCBDTH-UHFFFAOYSA-N 6-chloro-3-methylpyridine-2-carboxamide Chemical compound ClC1=CC=C(C(=N1)C(N)=O)C NPNSDEDMKCBDTH-UHFFFAOYSA-N 0.000 description 2
- VNFOGPPUEDURQA-UHFFFAOYSA-N 6-chloro-4-methylpyrido[3,2-d]pyrimidine Chemical compound C1=C(Cl)N=C2C(C)=NC=NC2=C1 VNFOGPPUEDURQA-UHFFFAOYSA-N 0.000 description 2
- QPYPQWUXCWISAT-UHFFFAOYSA-N 6-chloropyrido[3,2-d]pyrimidin-4-amine Chemical compound C1=C(Cl)N=C2C(N)=NC=NC2=C1 QPYPQWUXCWISAT-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108700003785 Baculoviral IAP Repeat-Containing 3 Proteins 0.000 description 2
- 102100021662 Baculoviral IAP repeat-containing protein 3 Human genes 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- OKSAIQYADDDIJR-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)Cl)C(F)(F)F Chemical compound BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)Cl)C(F)(F)F OKSAIQYADDDIJR-UHFFFAOYSA-N 0.000 description 2
- ZDIGYIAIWBRVND-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2C)N)C Chemical compound BrC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2C)N)C ZDIGYIAIWBRVND-UHFFFAOYSA-N 0.000 description 2
- DKJGUPHZVQYGNZ-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)N Chemical compound BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)N DKJGUPHZVQYGNZ-UHFFFAOYSA-N 0.000 description 2
- YAGPTMAECFJIHO-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(NC=C2)=O Chemical compound BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(NC=C2)=O YAGPTMAECFJIHO-UHFFFAOYSA-N 0.000 description 2
- ORUIJDZHOAWJNS-UHFFFAOYSA-N BrC=1C=C2C(=NC=NC2=C(C=1)I)NCC1=C(C=C(C=C1)OC)OC Chemical compound BrC=1C=C2C(=NC=NC2=C(C=1)I)NCC1=C(C=C(C=C1)OC)OC ORUIJDZHOAWJNS-UHFFFAOYSA-N 0.000 description 2
- XPQIFPFGUGWQNB-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)Cl)CC(C)C Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)Cl)CC(C)C XPQIFPFGUGWQNB-UHFFFAOYSA-N 0.000 description 2
- PXUONJQLVWDZCN-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)N)C Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)N)C PXUONJQLVWDZCN-UHFFFAOYSA-N 0.000 description 2
- QUVIXGGTCGQLJT-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)OC Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)OC QUVIXGGTCGQLJT-UHFFFAOYSA-N 0.000 description 2
- SWFQLTDEYXABLX-UHFFFAOYSA-N C(#C)C1(CCCC=2C=CC=NC1=2)O Chemical compound C(#C)C1(CCCC=2C=CC=NC1=2)O SWFQLTDEYXABLX-UHFFFAOYSA-N 0.000 description 2
- OMZUOIKLOAZGAC-QMMMGPOBSA-N C(#C)[C@@]1(CCN2C1=NC=C2)O Chemical compound C(#C)[C@@]1(CCN2C1=NC=C2)O OMZUOIKLOAZGAC-QMMMGPOBSA-N 0.000 description 2
- VGNUDSHOXJFGAB-CMDGGOBGSA-N C(C1=CC=CC=C1)OC=1C=C(C(=O)N)C(=CN=1)\C=C\OCC Chemical compound C(C1=CC=CC=C1)OC=1C=C(C(=O)N)C(=CN=1)\C=C\OCC VGNUDSHOXJFGAB-CMDGGOBGSA-N 0.000 description 2
- NAQHXVWBMCXWEJ-UHFFFAOYSA-N CC=1C2=C(N=C(N=1)SC)C(=NC=C2C)N Chemical compound CC=1C2=C(N=C(N=1)SC)C(=NC=C2C)N NAQHXVWBMCXWEJ-UHFFFAOYSA-N 0.000 description 2
- ULIKYCNITLBMGE-MRVPVSSYSA-N CC=1N=C(SC=1)[C@@](C)(C#C)O Chemical compound CC=1N=C(SC=1)[C@@](C)(C#C)O ULIKYCNITLBMGE-MRVPVSSYSA-N 0.000 description 2
- CYKRWPBBZNKEFA-UHFFFAOYSA-N CC=1N=CSC=1C(C)(C#C)O Chemical compound CC=1N=CSC=1C(C)(C#C)O CYKRWPBBZNKEFA-UHFFFAOYSA-N 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- RKJOSOCBDGSTIJ-SSDOTTSWSA-N CN1CC[C@](O)(C#C)C1=O Chemical compound CN1CC[C@](O)(C#C)C1=O RKJOSOCBDGSTIJ-SSDOTTSWSA-N 0.000 description 2
- MTHZKFNVVRCFRA-UHFFFAOYSA-N COC1=C(CNC2=NC=CC3=C2N=C(NC3=O)C2=CC(=CC=C2)I)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=CC3=C2N=C(NC3=O)C2=CC(=CC=C2)I)C=CC(=C1)OC MTHZKFNVVRCFRA-UHFFFAOYSA-N 0.000 description 2
- ROUXKTKPXBVWFU-LJAQVGFWSA-N COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2C)C#C[C@]2(C(N(CC2)C)=O)O)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2C)C#C[C@]2(C(N(CC2)C)=O)O)C=CC(=C1)OC ROUXKTKPXBVWFU-LJAQVGFWSA-N 0.000 description 2
- UADSBRUSLKILDW-LJAQVGFWSA-N COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2OC)C#C[C@]2(C(N(CC2)C)=O)O)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2OC)C#C[C@]2(C(N(CC2)C)=O)O)C=CC(=C1)OC UADSBRUSLKILDW-LJAQVGFWSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- AVSGMVDUWQAKCI-UHFFFAOYSA-N Cl.NCC1=C(C(=NC=C1)Cl)N Chemical compound Cl.NCC1=C(C(=NC=C1)Cl)N AVSGMVDUWQAKCI-UHFFFAOYSA-N 0.000 description 2
- XLLYYFMPBTZHLV-UHFFFAOYSA-N ClC=1C2=C(N=C(N=1)C1=CC(=CC=C1)I)C(=NC=C2)Cl Chemical compound ClC=1C2=C(N=C(N=1)C1=CC(=CC=C1)I)C(=NC=C2)Cl XLLYYFMPBTZHLV-UHFFFAOYSA-N 0.000 description 2
- DXOKGZCLGNRIJM-UHFFFAOYSA-N ClC=1C2=C(N=CN=1)OC(=N2)C1=CC(=CC=C1)I Chemical compound ClC=1C2=C(N=CN=1)OC(=N2)C1=CC(=CC=C1)I DXOKGZCLGNRIJM-UHFFFAOYSA-N 0.000 description 2
- LNGIYWQMEJXWIR-UHFFFAOYSA-N ClC=1C=CC=2N=C(N=C(C=2N=1)N)C(F)(F)F Chemical compound ClC=1C=CC=2N=C(N=C(C=2N=1)N)C(F)(F)F LNGIYWQMEJXWIR-UHFFFAOYSA-N 0.000 description 2
- PCINXBURUJCKEQ-UHFFFAOYSA-N ClC=1C=CC=2N=C(N=C(C=2N=1)N)C1CC1 Chemical compound ClC=1C=CC=2N=C(N=C(C=2N=1)N)C1CC1 PCINXBURUJCKEQ-UHFFFAOYSA-N 0.000 description 2
- QPYPQWUXCWISAT-WFVSFCRTSA-N ClC=1C=CC=2N=C(N=C(C=2N=1)N)[2H] Chemical compound ClC=1C=CC=2N=C(N=C(C=2N=1)N)[2H] QPYPQWUXCWISAT-WFVSFCRTSA-N 0.000 description 2
- WQUYFOCCVUZFOX-UHFFFAOYSA-N ClC=1C=CC=2N=CN=C(C=2N=1)OCC Chemical compound ClC=1C=CC=2N=CN=C(C=2N=1)OCC WQUYFOCCVUZFOX-UHFFFAOYSA-N 0.000 description 2
- FTNJEGHTUZAKGV-UHFFFAOYSA-N ClC=1N=C(C=2N=C(N=C(C=2N=1)N)C)C Chemical compound ClC=1N=C(C=2N=C(N=C(C=2N=1)N)C)C FTNJEGHTUZAKGV-UHFFFAOYSA-N 0.000 description 2
- HNPYFNFNUQMCFP-UHFFFAOYSA-N ClC=1N=C(C=2N=CN=C(C=2N=1)N)C Chemical compound ClC=1N=C(C=2N=CN=C(C=2N=1)N)C HNPYFNFNUQMCFP-UHFFFAOYSA-N 0.000 description 2
- UVGNHCYXHPCHDV-UHFFFAOYSA-N ClC=1N=CC=2N=C(N=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)C Chemical compound ClC=1N=CC=2N=C(N=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)C UVGNHCYXHPCHDV-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- ZRHIWSGAMBUDGD-SSDOTTSWSA-N FC(C=1N=C(SC=1)[C@@](C)(C#C)O)(F)F Chemical compound FC(C=1N=C(SC=1)[C@@](C)(C#C)O)(F)F ZRHIWSGAMBUDGD-SSDOTTSWSA-N 0.000 description 2
- SDHRHZSCUJFAJK-UHFFFAOYSA-N FC(S(=O)(=O)OC1=CCC(C1=O)(C)C)(F)F Chemical compound FC(S(=O)(=O)OC1=CCC(C1=O)(C)C)(F)F SDHRHZSCUJFAJK-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 101000617805 Homo sapiens Staphylococcal nuclease domain-containing protein 1 Proteins 0.000 description 2
- 101000830894 Homo sapiens Targeting protein for Xklp2 Proteins 0.000 description 2
- WHMOZJRPJSISBQ-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC2=C(N=CNC2=O)C(=N1)C Chemical compound IC=1C=C(C=CC=1)C1=CC2=C(N=CNC2=O)C(=N1)C WHMOZJRPJSISBQ-UHFFFAOYSA-N 0.000 description 2
- ZXJDPZJFKHWONG-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2)N Chemical compound IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2)N ZXJDPZJFKHWONG-UHFFFAOYSA-N 0.000 description 2
- KLYSIVMAWRUICZ-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2)[N+](=O)[O-] Chemical compound IC=1C=C(C=CC=1)C1=CC=C2C(=N1)C(=NN2)[N+](=O)[O-] KLYSIVMAWRUICZ-UHFFFAOYSA-N 0.000 description 2
- XZHHWOCGZXXIAN-UHFFFAOYSA-N IC=1C=C(C=CC=1)C1=NC=C2C=CNC(C2=C1)=O Chemical compound IC=1C=C(C=CC=1)C1=NC=C2C=CNC(C2=C1)=O XZHHWOCGZXXIAN-UHFFFAOYSA-N 0.000 description 2
- NDVCKFYXVWGURW-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)C Chemical compound IC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)C NDVCKFYXVWGURW-UHFFFAOYSA-N 0.000 description 2
- RMXRGIHXBDMNRW-WHRKIXHSSA-N IC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)[2H] Chemical compound IC=1C=C(C=CC=1)C=1C=CC=2N=C(N=C(C=2N=1)N)[2H] RMXRGIHXBDMNRW-WHRKIXHSSA-N 0.000 description 2
- ZRMQPYNANBDIQD-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C Chemical compound IC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C ZRMQPYNANBDIQD-UHFFFAOYSA-N 0.000 description 2
- JXWJDOSHHFOYSS-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1SC2=C(C=[N+](C=C2)[O-])N=1 Chemical compound IC=1C=C(C=CC=1)C=1SC2=C(C=[N+](C=C2)[O-])N=1 JXWJDOSHHFOYSS-UHFFFAOYSA-N 0.000 description 2
- OCNUTKBRTPMSSG-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1SC=2N=CN=C(C=2N=1)N Chemical compound IC=1C=C(C=CC=1)C=1SC=2N=CN=C(C=2N=1)N OCNUTKBRTPMSSG-UHFFFAOYSA-N 0.000 description 2
- VOHLYZQYTWVRKU-UHFFFAOYSA-N IC=1C=C(C=CC=1)N1CCC=2C=CN=C(C=2C1)N Chemical compound IC=1C=C(C=CC=1)N1CCC=2C=CN=C(C=2C1)N VOHLYZQYTWVRKU-UHFFFAOYSA-N 0.000 description 2
- AWVKJRLQVZHXQI-UHFFFAOYSA-N IC=1C=CC(=C(C=1)C1=CC=C2C=CN=C(C2=C1)N)C Chemical compound IC=1C=CC(=C(C=1)C1=CC=C2C=CN=C(C2=C1)N)C AWVKJRLQVZHXQI-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- ZPIFAILAPDHXIO-UHFFFAOYSA-N NC=1C(=NC=C(C=1C=O)C)Cl Chemical compound NC=1C(=NC=C(C=1C=O)C)Cl ZPIFAILAPDHXIO-UHFFFAOYSA-N 0.000 description 2
- LDLNXHCQIDIKGV-UHFFFAOYSA-N NC=1C(=NC=CC=1C(C(C)C)=O)Cl Chemical compound NC=1C(=NC=CC=1C(C(C)C)=O)Cl LDLNXHCQIDIKGV-UHFFFAOYSA-N 0.000 description 2
- PUKNSBRKWMCMBE-UHFFFAOYSA-N NC=1C(=NC=CC=1C(C(F)(F)F)(O)O)Cl Chemical compound NC=1C(=NC=CC=1C(C(F)(F)F)(O)O)Cl PUKNSBRKWMCMBE-UHFFFAOYSA-N 0.000 description 2
- HSXMDAPUPKUPMS-UHFFFAOYSA-N NC=1C2=C(N=C(N=1)CO)C=CC(=N2)Cl Chemical compound NC=1C2=C(N=C(N=1)CO)C=CC(=N2)Cl HSXMDAPUPKUPMS-UHFFFAOYSA-N 0.000 description 2
- LJGVSTKZALQANF-NRFANRHFSA-N NC=1C2=C(N=CN=1)C(=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C Chemical compound NC=1C2=C(N=CN=1)C(=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C LJGVSTKZALQANF-NRFANRHFSA-N 0.000 description 2
- AYNBOXCDQHBCBF-NRFANRHFSA-N NC=1N=CC=C2CCN(CC=12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1N=CC=C2CCN(CC=12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O AYNBOXCDQHBCBF-NRFANRHFSA-N 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- WIHGPPQWLLEOOJ-JTQLQIEISA-N O[C@]1(CCc2cccnc12)C#C Chemical compound O[C@]1(CCc2cccnc12)C#C WIHGPPQWLLEOOJ-JTQLQIEISA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 101100379220 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) API2 gene Proteins 0.000 description 2
- 101000942603 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Condensin complex subunit 3 Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 102000004399 TNF receptor-associated factor 3 Human genes 0.000 description 2
- 108090000922 TNF receptor-associated factor 3 Proteins 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 101000963191 Xenopus laevis Maternal DNA replication licensing factor mcm3 Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- WIKQEUJFZPCFNJ-UHFFFAOYSA-N carbonic acid;silver Chemical compound [Ag].[Ag].OC(O)=O WIKQEUJFZPCFNJ-UHFFFAOYSA-N 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 101150116749 chuk gene Proteins 0.000 description 2
- BKFAZDGHFACXKY-UHFFFAOYSA-N cobalt(II) bis(acetylacetonate) Chemical compound [Co+2].CC(=O)[CH-]C(C)=O.CC(=O)[CH-]C(C)=O BKFAZDGHFACXKY-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- UKAJDOBPPOAZSS-UHFFFAOYSA-N ethyl(trimethyl)silane Chemical compound CC[Si](C)(C)C UKAJDOBPPOAZSS-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229960004275 glycolic acid Drugs 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- QADKCSNOHBWQNO-UHFFFAOYSA-N methyl 2-hydroxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate Chemical compound COC(=O)C(O)CCNC(=O)OC(C)(C)C QADKCSNOHBWQNO-UHFFFAOYSA-N 0.000 description 2
- GQTSDNNJZKLQTK-UHFFFAOYSA-N methyl 3-amino-4-bromo-6-chloropyridine-2-carboxylate Chemical compound COC(=O)C1=NC(Cl)=CC(Br)=C1N GQTSDNNJZKLQTK-UHFFFAOYSA-N 0.000 description 2
- LSAOMLGJMYNCOV-UHFFFAOYSA-N methyl 3-amino-4-methyl-6-(3-trimethylsilylphenyl)pyridine-2-carboxylate Chemical compound NC=1C(=NC(=CC=1C)C1=CC(=CC=C1)[Si](C)(C)C)C(=O)OC LSAOMLGJMYNCOV-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 description 2
- YPOXGDJGKBXRFP-UHFFFAOYSA-M pyrimidine-4-carboxylate Chemical compound [O-]C(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-M 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 2
- KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 229960004274 stearic acid Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- KFURVOPCCFERLA-UHFFFAOYSA-N tert-butyl N-[2-chloro-4-(2,2,2-trifluoro-1,1-dihydroxyethyl)pyridin-3-yl]carbamate Chemical compound ClC1=NC=CC(=C1NC(OC(C)(C)C)=O)C(C(F)(F)F)(O)O KFURVOPCCFERLA-UHFFFAOYSA-N 0.000 description 2
- RHAUUZRWGHXLJB-UHFFFAOYSA-N tert-butyl n-(2-chloro-5-methylpyridin-3-yl)carbamate Chemical compound CC1=CN=C(Cl)C(NC(=O)OC(C)(C)C)=C1 RHAUUZRWGHXLJB-UHFFFAOYSA-N 0.000 description 2
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- PNFABLYULYBMJL-UHFFFAOYSA-N trimethyl-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]silane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC([Si](C)(C)C)=C1 PNFABLYULYBMJL-UHFFFAOYSA-N 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- HNNNMXCXTVTFCK-HXUWFJFHSA-N (2R)-2-(2-methyl-1,3-thiazol-5-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC=1SC(=CN=1)[C@@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O HNNNMXCXTVTFCK-HXUWFJFHSA-N 0.000 description 1
- LWYVPDIEPCWPFB-HXUWFJFHSA-N (2R)-2-(4-methyl-1,3-thiazol-5-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC=1N=CSC=1[C@@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O LWYVPDIEPCWPFB-HXUWFJFHSA-N 0.000 description 1
- LQXQIDZSESAZDP-HXUWFJFHSA-N (2R)-2-(5-methyl-1,2-oxazol-3-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC1=CC(=NO1)[C@@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O LQXQIDZSESAZDP-HXUWFJFHSA-N 0.000 description 1
- YCCRSQHGHNGFTN-HXUWFJFHSA-N (2R)-2-(5-methyl-1,3-thiazol-2-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC1=CN=C(S1)[C@@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O YCCRSQHGHNGFTN-HXUWFJFHSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- XRGCRZJWNOATJE-NRFANRHFSA-N (2R)-2-hydroxy-5,5-dimethyl-2-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]cyclopentan-1-one Chemical compound O[C@@]1(C(C(CC1)(C)C)=O)C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C XRGCRZJWNOATJE-NRFANRHFSA-N 0.000 description 1
- LWYVPDIEPCWPFB-FQEVSTJZSA-N (2S)-2-(4-methyl-1,3-thiazol-5-yl)-4-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-3-yn-2-ol Chemical compound CC=1N=CSC=1[C@](C)(C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)O LWYVPDIEPCWPFB-FQEVSTJZSA-N 0.000 description 1
- XRGCRZJWNOATJE-OAQYLSRUSA-N (2S)-2-hydroxy-5,5-dimethyl-2-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]cyclopentan-1-one Chemical compound O[C@]1(C(C(CC1)(C)C)=O)C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C XRGCRZJWNOATJE-OAQYLSRUSA-N 0.000 description 1
- SUYJXERPRICYRX-UHFFFAOYSA-N (3-bromophenyl)methanamine Chemical compound NCC1=CC=CC(Br)=C1 SUYJXERPRICYRX-UHFFFAOYSA-N 0.000 description 1
- REEUXWXIMNEIIN-UHFFFAOYSA-N (3-iodophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(I)=C1 REEUXWXIMNEIIN-UHFFFAOYSA-N 0.000 description 1
- LQLOGZQVKUNBRX-UHFFFAOYSA-N (3-iodophenyl)methanamine Chemical compound NCC1=CC=CC(I)=C1 LQLOGZQVKUNBRX-UHFFFAOYSA-N 0.000 description 1
- SYDSHTZOHFOVFO-FQEVSTJZSA-N (3R)-3-[2-[3-(4-aminopyrido[3,2-d]pyrimidin-6-yl)phenyl]ethynyl]-3-hydroxy-1-methylpyrrolidin-2-one Chemical compound NC=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O SYDSHTZOHFOVFO-FQEVSTJZSA-N 0.000 description 1
- FKVSVHKPLBGNQS-ZNCSYKOHSA-N (3R)-3-[2-[3-(8-aminopyrido[3,4-d]pyrimidin-2-yl)phenyl]ethynyl]-3-hydroxy-1-(trideuteriomethyl)pyrrolidin-2-one Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C([2H])([2H])[2H])=O)O FKVSVHKPLBGNQS-ZNCSYKOHSA-N 0.000 description 1
- OYCLKJFNFRJGOD-OHPOIYDLSA-N (3S)-3-[2-[3-(2-deuterio-4-imino-1H-pyrido[3,2-d]pyrimidin-6-yl)phenyl]ethynyl]-3-hydroxy-1-methylpiperidin-2-one Chemical compound NC=1C2=C(N=C(N=1)[2H])C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CCC1)C)=O)O OYCLKJFNFRJGOD-OHPOIYDLSA-N 0.000 description 1
- FVRLSHRAYPFXRQ-UHFFFAOYSA-N (5-bromo-2-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(Br)C=C1B(O)O FVRLSHRAYPFXRQ-UHFFFAOYSA-N 0.000 description 1
- WCVYCWMKRJOZRS-UHFFFAOYSA-N (8-methyl-1,4-dioxaspiro[4.4]non-8-en-9-yl) acetate Chemical compound C(C)(=O)OC=1C2(OCCO2)CCC=1C WCVYCWMKRJOZRS-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- QWEWLLNSJDTOKH-UHFFFAOYSA-N 1,3-thiazole-2-carboxamide Chemical compound NC(=O)C1=NC=CS1 QWEWLLNSJDTOKH-UHFFFAOYSA-N 0.000 description 1
- VOJUXHHACRXLTD-UHFFFAOYSA-N 1,4-dihydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC(O)=C21 VOJUXHHACRXLTD-UHFFFAOYSA-N 0.000 description 1
- QIHKZFPXCRBYTG-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)pyrrolidine-2,3-dione Chemical compound FC(F)(F)CN1CCC(=O)C1=O QIHKZFPXCRBYTG-UHFFFAOYSA-N 0.000 description 1
- UJIGIKQKDDJTJL-UHFFFAOYSA-N 1-(2-methyl-1,3-thiazol-4-yl)ethanone Chemical compound CC(=O)C1=CSC(C)=N1 UJIGIKQKDDJTJL-UHFFFAOYSA-N 0.000 description 1
- KYVXYWKQFCSMHL-UHFFFAOYSA-N 1-(5-methyl-1,2-oxazol-3-yl)ethanone Chemical compound CC(=O)C=1C=C(C)ON=1 KYVXYWKQFCSMHL-UHFFFAOYSA-N 0.000 description 1
- JXQWNDZCRUPING-UHFFFAOYSA-N 1-bromo-2-methylpropane;zinc Chemical compound [Zn].CC(C)CBr JXQWNDZCRUPING-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- NUIPHLLHBOONMC-UHFFFAOYSA-N 1-methyl-3-phenylmethoxypyridin-2-one Chemical compound O=C1N(C)C=CC=C1OCC1=CC=CC=C1 NUIPHLLHBOONMC-UHFFFAOYSA-N 0.000 description 1
- DNMTXRJELGPOGW-UHFFFAOYSA-N 1-methylindazole-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2N(C)N=CC2=C1 DNMTXRJELGPOGW-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- HSPVTPHRQMNTQW-UHFFFAOYSA-N 1-nitroprop-1-en-2-amine Chemical compound CC(N)=C[N+]([O-])=O HSPVTPHRQMNTQW-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- UIGLAZDLBZDVBL-UHFFFAOYSA-N 1-phenylprop-2-yn-1-ol Chemical class C#CC(O)C1=CC=CC=C1 UIGLAZDLBZDVBL-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- JDBJZZTZYKUFFK-UHFFFAOYSA-N 2,2,2-trifluoro-n-methoxy-n-methylacetamide Chemical compound CON(C)C(=O)C(F)(F)F JDBJZZTZYKUFFK-UHFFFAOYSA-N 0.000 description 1
- NITMACBPVVUGOJ-UHFFFAOYSA-N 2,2,2-trifluoroethanimidamide Chemical compound NC(=N)C(F)(F)F NITMACBPVVUGOJ-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- PRAFLUMTYHBEHE-UHFFFAOYSA-N 2,6-dimethyl-1h-pyridin-4-one Chemical compound CC1=CC(O)=CC(C)=N1 PRAFLUMTYHBEHE-UHFFFAOYSA-N 0.000 description 1
- YFTHTJAPODJVSL-UHFFFAOYSA-N 2-(1-benzothiophen-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(SC=C2)C2=C1 YFTHTJAPODJVSL-UHFFFAOYSA-N 0.000 description 1
- OJFUEYPIGJFQBO-UHFFFAOYSA-N 2-(2-methyl-1,3-thiazol-5-yl)-4-trimethylsilylbut-3-yn-2-ol Chemical compound CC=1SC(=CN=1)C(C)(C#C[Si](C)(C)C)O OJFUEYPIGJFQBO-UHFFFAOYSA-N 0.000 description 1
- ULIKYCNITLBMGE-UHFFFAOYSA-N 2-(4-methyl-1,3-thiazol-2-yl)but-3-yn-2-ol Chemical compound CC1=CSC(C(C)(O)C#C)=N1 ULIKYCNITLBMGE-UHFFFAOYSA-N 0.000 description 1
- YAHLNIAKBFYRMV-UHFFFAOYSA-N 2-(5-bromo-2-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound COC1=CC=C(Br)C=C1B1OC(C)(C)C(C)(C)O1 YAHLNIAKBFYRMV-UHFFFAOYSA-N 0.000 description 1
- CIFYKKUUTOSOIK-UHFFFAOYSA-N 2-(5-bromo-2-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1=CC=C(Br)C=C1B1OC(C)(C)C(C)(C)O1 CIFYKKUUTOSOIK-UHFFFAOYSA-N 0.000 description 1
- YUGDGZWIUSSLGX-UHFFFAOYSA-N 2-(5-methyl-1,2-oxazol-3-yl)but-3-yn-2-ol Chemical compound CC1=CC(C(C)(O)C#C)=NO1 YUGDGZWIUSSLGX-UHFFFAOYSA-N 0.000 description 1
- AJKVQEKCUACUMD-UHFFFAOYSA-N 2-Acetylpyridine Chemical compound CC(=O)C1=CC=CC=N1 AJKVQEKCUACUMD-UHFFFAOYSA-N 0.000 description 1
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical compound CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- MRAYNLYCQPAZJN-BQYQJAHWSA-N 2-[(e)-2-ethoxyethenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CCO\C=C\B1OC(C)(C)C(C)(C)O1 MRAYNLYCQPAZJN-BQYQJAHWSA-N 0.000 description 1
- MPENGIRQVIQXNS-UHFFFAOYSA-N 2-[4-(trifluoromethyl)-1,3-thiazol-2-yl]-4-trimethylsilylbut-3-yn-2-ol Chemical compound FC(C=1N=C(SC=1)C(C)(C#C[Si](C)(C)C)O)(F)F MPENGIRQVIQXNS-UHFFFAOYSA-N 0.000 description 1
- CQKIBEOVARIBDN-UHFFFAOYSA-N 2-chloro-5-methylpyridin-3-amine Chemical compound CC1=CN=C(Cl)C(N)=C1 CQKIBEOVARIBDN-UHFFFAOYSA-N 0.000 description 1
- VXFREJOQLWBEKN-UHFFFAOYSA-N 2-chloro-6-methylpyridine-4-carbaldehyde Chemical compound CC1=CC(C=O)=CC(Cl)=N1 VXFREJOQLWBEKN-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- 239000001837 2-hydroxy-3-methylcyclopent-2-en-1-one Substances 0.000 description 1
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
- ZHDRDZMTEOIWSX-UHFFFAOYSA-N 2-methyl-1,3-thiazole-4-carboxylic acid Chemical compound CC1=NC(C(O)=O)=CS1 ZHDRDZMTEOIWSX-UHFFFAOYSA-N 0.000 description 1
- GDAZZZLHHSQPOQ-UHFFFAOYSA-N 2-methyl-3-phenyloxaziridine Chemical compound CN1OC1C1=CC=CC=C1 GDAZZZLHHSQPOQ-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- SNKQUAATTWNZCV-UHFFFAOYSA-N 2-pyridin-2-ylbut-3-yn-2-ol Chemical compound C#CC(O)(C)C1=CC=CC=N1 SNKQUAATTWNZCV-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- GIVIUOKNKXIFQD-UHFFFAOYSA-N 3-(difluoromethyl)-1-methyl-3-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one Chemical compound FC(C1(C(N(CC1)C)=O)C#CC1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C)F GIVIUOKNKXIFQD-UHFFFAOYSA-N 0.000 description 1
- PYSMBZIYOFOUQA-UHFFFAOYSA-N 3-amino-2-methoxypyridine-4-carbaldehyde Chemical compound COC1=NC=CC(C=O)=C1N PYSMBZIYOFOUQA-UHFFFAOYSA-N 0.000 description 1
- ABVDQGNEDSKBLA-UHFFFAOYSA-N 3-amino-2-methoxypyridine-4-carboxylic acid Chemical compound COC1=NC=CC(C(O)=O)=C1N ABVDQGNEDSKBLA-UHFFFAOYSA-N 0.000 description 1
- XXCFWGIRIFRPER-UHFFFAOYSA-N 3-amino-6-bromopyrazine-2-carbonitrile Chemical compound NC1=NC=C(Br)N=C1C#N XXCFWGIRIFRPER-UHFFFAOYSA-N 0.000 description 1
- GGQNLFCQZACXET-UHFFFAOYSA-N 3-amino-6-chloropyridine-2-carbonitrile Chemical compound NC1=CC=C(Cl)N=C1C#N GGQNLFCQZACXET-UHFFFAOYSA-N 0.000 description 1
- FYEQKMAVRYRMBL-UHFFFAOYSA-N 3-aminopyridine-4-carboxylic acid Chemical compound NC1=CN=CC=C1C(O)=O FYEQKMAVRYRMBL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 1
- XUFKSABSPCNGCK-UHFFFAOYSA-N 3-bromo-4-chloro-2,6-dimethylpyridine Chemical compound CC1=CC(Cl)=C(Br)C(C)=N1 XUFKSABSPCNGCK-UHFFFAOYSA-N 0.000 description 1
- XIZFRYIWRFNILW-UHFFFAOYSA-N 3-bromobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CC(Br)=C1 XIZFRYIWRFNILW-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RKJOSOCBDGSTIJ-BMSJAHLVSA-N 3-ethynyl-3-hydroxy-1-(trideuteriomethyl)pyrrolidin-2-one Chemical compound [2H]C([2H])([2H])N1CCC(O)(C#C)C1=O RKJOSOCBDGSTIJ-BMSJAHLVSA-N 0.000 description 1
- FFCSRWGYGMRBGD-UHFFFAOYSA-N 3-iodoaniline Chemical compound NC1=CC=CC(I)=C1 FFCSRWGYGMRBGD-UHFFFAOYSA-N 0.000 description 1
- XJQGSJBTLSVOQF-UHFFFAOYSA-N 3-iodobenzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(I)=C1 XJQGSJBTLSVOQF-UHFFFAOYSA-N 0.000 description 1
- WHSXTWFYRGOBGO-UHFFFAOYSA-N 3-methylsalicylic acid Chemical compound CC1=CC=CC(C(O)=O)=C1O WHSXTWFYRGOBGO-UHFFFAOYSA-N 0.000 description 1
- CKPNVNAKQGYUSK-UHFFFAOYSA-N 4,6-dichloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1Cl CKPNVNAKQGYUSK-UHFFFAOYSA-N 0.000 description 1
- NIGDWBHWHVHOAD-UHFFFAOYSA-N 4,6-dichloropyrimidin-5-amine Chemical compound NC1=C(Cl)N=CN=C1Cl NIGDWBHWHVHOAD-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- PKRKJRIVVOGXHM-UHFFFAOYSA-N 4-amino-1h-pyrazole-5-carbonitrile Chemical compound NC=1C=NNC=1C#N PKRKJRIVVOGXHM-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- MQZDYWUQGYYENI-UHFFFAOYSA-N 4-aminoquinazoline-6,8-dicarbonitrile Chemical compound NC1=NC=NC2=C(C=C(C=C12)C#N)C#N MQZDYWUQGYYENI-UHFFFAOYSA-N 0.000 description 1
- IVUOMFWNDGNLBJ-UHFFFAOYSA-N 4-azaniumyl-2-hydroxybutanoate Chemical compound NCCC(O)C(O)=O IVUOMFWNDGNLBJ-UHFFFAOYSA-N 0.000 description 1
- GTLFLMZOABSJSV-UHFFFAOYSA-N 4-chloropyridin-3-amine Chemical compound NC1=CN=CC=C1Cl GTLFLMZOABSJSV-UHFFFAOYSA-N 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- HPNBWHDRLCVZFV-UHFFFAOYSA-N 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound CC1=CC=C(N)C=C1B1OC(C)(C)C(C)(C)O1 HPNBWHDRLCVZFV-UHFFFAOYSA-N 0.000 description 1
- XHTRHEMAXFRQDD-UHFFFAOYSA-N 4-methyl-N-(4-methylbenzoyl)iminobenzamide Chemical compound C1=CC(C)=CC=C1C(=O)N=NC(=O)C1=CC=C(C)C=C1 XHTRHEMAXFRQDD-UHFFFAOYSA-N 0.000 description 1
- AOLGPUHMHFJSJQ-UHFFFAOYSA-N 5,6,7,8-tetrahydro-2,7-naphthyridin-1-amine Chemical compound C1CNCC2=C1C=CN=C2N AOLGPUHMHFJSJQ-UHFFFAOYSA-N 0.000 description 1
- ZYTSUWIWLUKHJR-UHFFFAOYSA-N 5,6-diamino-2-methyl-1h-pyrimidin-4-one Chemical compound CC1=NC(=O)C(N)=C(N)N1 ZYTSUWIWLUKHJR-UHFFFAOYSA-N 0.000 description 1
- NDMZZQRNZFWMEZ-UHFFFAOYSA-N 5-bromo-1h-pyridin-2-one Chemical compound OC1=CC=C(Br)C=N1 NDMZZQRNZFWMEZ-UHFFFAOYSA-N 0.000 description 1
- ZXYNLEUXPBAEIL-UHFFFAOYSA-N 5-bromo-2,6-dimethyl-1h-pyrimidin-4-one Chemical compound CC1=NC(C)=C(Br)C(O)=N1 ZXYNLEUXPBAEIL-UHFFFAOYSA-N 0.000 description 1
- GYCNHFWRPJXTSB-UHFFFAOYSA-N 5-bromo-2-fluorobenzonitrile Chemical compound FC1=CC=C(Br)C=C1C#N GYCNHFWRPJXTSB-UHFFFAOYSA-N 0.000 description 1
- JIGKPMMZNMQXDL-UHFFFAOYSA-N 5-bromo-2-iodobenzonitrile Chemical compound BrC1=CC=C(I)C(C#N)=C1 JIGKPMMZNMQXDL-UHFFFAOYSA-N 0.000 description 1
- PYZUYYOYVZFJGX-UHFFFAOYSA-N 5-chloro-1h-pyrazolo[4,3-b]pyridine Chemical compound ClC1=CC=C2NN=CC2=N1 PYZUYYOYVZFJGX-UHFFFAOYSA-N 0.000 description 1
- FVEBPHMWZVPXQS-UHFFFAOYSA-N 5-iodo-2-methoxybenzoic acid Chemical compound COC1=CC=C(I)C=C1C(O)=O FVEBPHMWZVPXQS-UHFFFAOYSA-N 0.000 description 1
- WUBHOZQZSHGUFI-UHFFFAOYSA-N 5-iodo-2-methylbenzoic acid Chemical compound CC1=CC=C(I)C=C1C(O)=O WUBHOZQZSHGUFI-UHFFFAOYSA-N 0.000 description 1
- WKRKOJKYDUWPTQ-UHFFFAOYSA-N 5-iodo-2-methylbenzoyl chloride Chemical compound CC1=CC=C(I)C=C1C(Cl)=O WKRKOJKYDUWPTQ-UHFFFAOYSA-N 0.000 description 1
- NEACBPHJNVVONN-UHFFFAOYSA-N 6,6-dichlorohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1PCCCCCC(Cl)Cl NEACBPHJNVVONN-UHFFFAOYSA-N 0.000 description 1
- JIAKIQWNYAZUJD-UHFFFAOYSA-N 6,7-dihydro-5h-quinolin-8-one Chemical compound C1=CN=C2C(=O)CCCC2=C1 JIAKIQWNYAZUJD-UHFFFAOYSA-N 0.000 description 1
- RXOCJQZPMNEQJD-UHFFFAOYSA-N 6-bromo-4-chloropyrido[2,3-d]pyrimidine Chemical compound C1=C(Br)C=C2C(Cl)=NC=NC2=N1 RXOCJQZPMNEQJD-UHFFFAOYSA-N 0.000 description 1
- FHCKWLXHKAPOBN-UHFFFAOYSA-N 6-bromoquinazolin-4-amine Chemical compound C1=C(Br)C=C2C(N)=NC=NC2=C1 FHCKWLXHKAPOBN-UHFFFAOYSA-N 0.000 description 1
- QHJNXFUNGGUIDH-UHFFFAOYSA-N 6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=C(Cl)C=C2C(N)=NC=NC2=C1 QHJNXFUNGGUIDH-UHFFFAOYSA-N 0.000 description 1
- OCOHPSHRDKBGOZ-UHFFFAOYSA-N 6-methyl-2-methylsulfanyl-1h-pyrimidin-4-one Chemical compound CSC1=NC(=O)C=C(C)N1 OCOHPSHRDKBGOZ-UHFFFAOYSA-N 0.000 description 1
- AVUWNHRPNQVSOI-UHFFFAOYSA-N 6-methylsulfanyl-1h-pyrimido[5,4-d]pyrimidin-4-one Chemical compound N1C=NC(=O)C2=NC(SC)=NC=C21 AVUWNHRPNQVSOI-UHFFFAOYSA-N 0.000 description 1
- PLOCDXILPIGHEZ-UHFFFAOYSA-N 7-bromoisoquinolin-1-amine Chemical compound C1=C(Br)C=C2C(N)=NC=CC2=C1 PLOCDXILPIGHEZ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 1
- 108010046304 B-Cell Activation Factor Receptor Proteins 0.000 description 1
- 102000007536 B-Cell Activation Factor Receptor Human genes 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical group NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101150104237 Birc3 gene Proteins 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- DZQJNQDCHGCENV-UHFFFAOYSA-N BrC1=NC=C(C2=C1N=C(N=C2C)SC)C Chemical compound BrC1=NC=C(C2=C1N=C(N=C2C)SC)C DZQJNQDCHGCENV-UHFFFAOYSA-N 0.000 description 1
- VWDJAXHELBFGPA-UHFFFAOYSA-N BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2C)Cl Chemical compound BrC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2C)Cl VWDJAXHELBFGPA-UHFFFAOYSA-N 0.000 description 1
- VBDCTPFDUXRPBG-UHFFFAOYSA-N BrC=1C=C2C(=NC=NC2=C(C=1)C)N Chemical compound BrC=1C=C2C(=NC=NC2=C(C=1)C)N VBDCTPFDUXRPBG-UHFFFAOYSA-N 0.000 description 1
- AFVJMFJBWJCKKM-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)NCC1=C(C=C(C=C1)OC)OC)CC(C)C Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC2=C(N=1)C(=NC=C2)NCC1=C(C=C(C=C1)OC)OC)CC(C)C AFVJMFJBWJCKKM-UHFFFAOYSA-N 0.000 description 1
- AOHAMSAYLBSRJR-UHFFFAOYSA-N BrC=1C=CC(=C(C=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)C Chemical compound BrC=1C=CC(=C(C=1)C=1N=CC=2N=CN=C(C=2N=1)NCC1=C(C=C(C=C1)OC)OC)C AOHAMSAYLBSRJR-UHFFFAOYSA-N 0.000 description 1
- DEWINFSGUMWZTN-UHFFFAOYSA-N C(#C)C1(C(C(CC1)(C)C)=O)O Chemical compound C(#C)C1(C(C(CC1)(C)C)=O)O DEWINFSGUMWZTN-UHFFFAOYSA-N 0.000 description 1
- OESHJQBZWYRHFY-UHFFFAOYSA-N C(#C)C1(C(N(CC1)CC(F)(F)F)=O)O Chemical compound C(#C)C1(C(N(CC1)CC(F)(F)F)=O)O OESHJQBZWYRHFY-UHFFFAOYSA-N 0.000 description 1
- OMZUOIKLOAZGAC-MRVPVSSYSA-N C(#C)[C@]1(CCN2C1=NC=C2)O Chemical compound C(#C)[C@]1(CCN2C1=NC=C2)O OMZUOIKLOAZGAC-MRVPVSSYSA-N 0.000 description 1
- KKNKLZRZMGRBNX-GKOSEXJESA-N C(C)(C)(C)OC(=O)N(CCC(C(=O)OC)=O)C([2H])([2H])[2H] Chemical compound C(C)(C)(C)OC(=O)N(CCC(C(=O)OC)=O)C([2H])([2H])[2H] KKNKLZRZMGRBNX-GKOSEXJESA-N 0.000 description 1
- UGVZYSVFHOKGCN-SNAWJCMRSA-N C(C)O/C=C/C=1C(=NC(=NC=1)SC)C(=O)N Chemical compound C(C)O/C=C/C=1C(=NC(=NC=1)SC)C(=O)N UGVZYSVFHOKGCN-SNAWJCMRSA-N 0.000 description 1
- OAGPADHFTUSRAR-UHFFFAOYSA-N CC=1C2=C(N=C(N=1)SC)C(NC=C2C)=O Chemical compound CC=1C2=C(N=C(N=1)SC)C(NC=C2C)=O OAGPADHFTUSRAR-UHFFFAOYSA-N 0.000 description 1
- HYFYTYDEDNPWIO-UHFFFAOYSA-N CC=1SC(=CN=1)C(C)(C#C)O Chemical compound CC=1SC(=CN=1)C(C)(C#C)O HYFYTYDEDNPWIO-UHFFFAOYSA-N 0.000 description 1
- HYFYTYDEDNPWIO-QMMMGPOBSA-N CC=1SC(=CN=1)[C@](C)(C#C)O Chemical compound CC=1SC(=CN=1)[C@](C)(C#C)O HYFYTYDEDNPWIO-QMMMGPOBSA-N 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- YQSYPBFCDXNNHE-MUUNZHRXSA-N COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@](C)(O)C=2SC=CN=2)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@](C)(O)C=2SC=CN=2)C=CC(=C1)OC YQSYPBFCDXNNHE-MUUNZHRXSA-N 0.000 description 1
- UIQIOWYWDLGQGO-HKBQPEDESA-N COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@]2(CCC=3C2=NC=CC=3)O)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@]2(CCC=3C2=NC=CC=3)O)C=CC(=C1)OC UIQIOWYWDLGQGO-HKBQPEDESA-N 0.000 description 1
- NNPRPRFLVLNSQI-LJAQVGFWSA-N COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@]2(CCN3C2=NC=C3)O)C=CC(=C1)OC Chemical compound COC1=C(CNC2=NC=NC3=C2N=C(N=C3)C=2C=C(C=CC=2)C#C[C@@]2(CCN3C2=NC=C3)O)C=CC(=C1)OC NNPRPRFLVLNSQI-LJAQVGFWSA-N 0.000 description 1
- JKRPQLKOLGLSET-UHFFFAOYSA-N CON(C(=O)C=1SC=C(N=1)C(F)(F)F)C Chemical compound CON(C(=O)C=1SC=C(N=1)C(F)(F)F)C JKRPQLKOLGLSET-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- MUSIXQBWJQYRLX-UHFFFAOYSA-N ClC=1C=CC=2N=C(N=C(C=2N=1)N)C Chemical compound ClC=1C=CC=2N=C(N=C(C=2N=1)N)C MUSIXQBWJQYRLX-UHFFFAOYSA-N 0.000 description 1
- YFJXNUCVAWQRMI-UHFFFAOYSA-N ClC=1C=CC=2N=C(N=C(C=2N=1)N)CF Chemical compound ClC=1C=CC=2N=C(N=C(C=2N=1)N)CF YFJXNUCVAWQRMI-UHFFFAOYSA-N 0.000 description 1
- CJIDUAUYTVBGHA-UHFFFAOYSA-N ClC=1N=CC=C2C=CC(=NC=12)C1=CC(=CC=C1)I Chemical compound ClC=1N=CC=C2C=CC(=NC=12)C1=CC(=CC=C1)I CJIDUAUYTVBGHA-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- FCDUODGTKYJMAI-UHFFFAOYSA-N FC(C1(C(N(CC1)C)=O)C(=O)OC)F Chemical compound FC(C1(C(N(CC1)C)=O)C(=O)OC)F FCDUODGTKYJMAI-UHFFFAOYSA-N 0.000 description 1
- ZRHIWSGAMBUDGD-UHFFFAOYSA-N FC(C=1N=C(SC=1)C(C)(C#C)O)(F)F Chemical compound FC(C=1N=C(SC=1)C(C)(C#C)O)(F)F ZRHIWSGAMBUDGD-UHFFFAOYSA-N 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- 101001005550 Homo sapiens Mitogen-activated protein kinase kinase kinase 14 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- RDHPBUTYVINBTL-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1C=C(C=2N=CN=C(C=2N=1)N)C Chemical compound IC=1C=C(C=CC=1)C=1C=C(C=2N=CN=C(C=2N=1)N)C RDHPBUTYVINBTL-UHFFFAOYSA-N 0.000 description 1
- BPNLVLVMCJFFRZ-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C(C)C Chemical compound IC=1C=C(C=CC=1)C=1N=C(C2=C(N=1)C(=NC=C2)N)C(C)C BPNLVLVMCJFFRZ-UHFFFAOYSA-N 0.000 description 1
- YOCOAXYDAZUECE-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)N Chemical compound IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(=NC=C2)N YOCOAXYDAZUECE-UHFFFAOYSA-N 0.000 description 1
- AJZAZTYTRDFWPO-UHFFFAOYSA-N IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(NC=C2)=O Chemical compound IC=1C=C(C=CC=1)C=1N=CC2=C(N=1)C(NC=C2)=O AJZAZTYTRDFWPO-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- LHPXYPROPRFEQE-UHFFFAOYSA-N Methylhalfordinol Chemical compound C1=CC(OC)=CC=C1C1=CN=C(C=2C=NC=CC=2)O1 LHPXYPROPRFEQE-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100025211 Mitogen-activated protein kinase kinase kinase 14 Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- VDIPNVCWMXZNFY-UHFFFAOYSA-N N-methyl-beta-alanine Chemical compound CNCCC(O)=O VDIPNVCWMXZNFY-UHFFFAOYSA-N 0.000 description 1
- QVVRJIVEXLKNQT-HSZRJFAPSA-N N1(CCC1)C1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O Chemical compound N1(CCC1)C1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)O QVVRJIVEXLKNQT-HSZRJFAPSA-N 0.000 description 1
- CIJLFNKWVKARDR-QHCPKHFHSA-N N1(CCC1)C=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound N1(CCC1)C=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O CIJLFNKWVKARDR-QHCPKHFHSA-N 0.000 description 1
- BLLMEWNSQSVGCC-UHFFFAOYSA-N N1(CCC1)C=1C2=C(N=CN=1)C=CC(=N2)Cl Chemical compound N1(CCC1)C=1C2=C(N=CN=1)C=CC(=N2)Cl BLLMEWNSQSVGCC-UHFFFAOYSA-N 0.000 description 1
- WZMWBPWJBQVZJW-FQEVSTJZSA-N NC1=NC(=NC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C Chemical compound NC1=NC(=NC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C WZMWBPWJBQVZJW-FQEVSTJZSA-N 0.000 description 1
- FKVSVHKPLBGNQS-MPTDGOKMSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O FKVSVHKPLBGNQS-MPTDGOKMSA-N 0.000 description 1
- ZNDBDENWXZSRTG-HXUWFJFHSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)CC(F)(F)F)=O)O Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)CC(F)(F)F)=O)O ZNDBDENWXZSRTG-HXUWFJFHSA-N 0.000 description 1
- ZNDBDENWXZSRTG-FQEVSTJZSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)CC(F)(F)F)=O)O Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)CC(F)(F)F)=O)O ZNDBDENWXZSRTG-FQEVSTJZSA-N 0.000 description 1
- DYSYUAMULMKFKB-OAQYLSRUSA-N NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1C)C#C[C@@](C)(O)C=1SC=CN=1 Chemical compound NC1=NC=CC2=C1N=C(N=C2)C=1C=C(C=CC=1C)C#C[C@@](C)(O)C=1SC=CN=1 DYSYUAMULMKFKB-OAQYLSRUSA-N 0.000 description 1
- LYEWZEZTFVTEPC-HSZRJFAPSA-N NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@@](C)(O)C=1SC=CN=1 Chemical compound NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@@](C)(O)C=1SC=CN=1 LYEWZEZTFVTEPC-HSZRJFAPSA-N 0.000 description 1
- OLNIYHYTHKDLLI-ZHBYIVLDSA-N NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O Chemical compound NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@@]1(C(N(CC1)C([2H])([2H])[2H])=O)O OLNIYHYTHKDLLI-ZHBYIVLDSA-N 0.000 description 1
- OLNIYHYTHKDLLI-ZPCYUGHHSA-N NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C([2H])([2H])[2H])=O)O Chemical compound NC1=NC=CC2=CC=C(C=C12)C=1C=C(C=CC=1C)C#C[C@]1(C(N(CC1)C([2H])([2H])[2H])=O)O OLNIYHYTHKDLLI-ZPCYUGHHSA-N 0.000 description 1
- KRMUOWIWZJSQSY-UHFFFAOYSA-N NC1=NC=NC(=C1NC(C1=C(C=CC(=C1)I)OC)=O)O Chemical compound NC1=NC=NC(=C1NC(C1=C(C=CC(=C1)I)OC)=O)O KRMUOWIWZJSQSY-UHFFFAOYSA-N 0.000 description 1
- BPZKZAWOIHMTJC-JOCHJYFZSA-N NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@@](C)(O)C1=NOC(=C1)C Chemical compound NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@@](C)(O)C1=NOC(=C1)C BPZKZAWOIHMTJC-JOCHJYFZSA-N 0.000 description 1
- REAFYHLZSHMRMO-OAQYLSRUSA-N NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@@](C)(O)C=1SC=CN=1 Chemical compound NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@@](C)(O)C=1SC=CN=1 REAFYHLZSHMRMO-OAQYLSRUSA-N 0.000 description 1
- MFUBQMZDXKAVSA-NRFANRHFSA-N NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=NC2=CC=C(C=C12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O MFUBQMZDXKAVSA-NRFANRHFSA-N 0.000 description 1
- XQFDFGOXRWRVQY-IBGZPJMESA-N NC1=NC=NC2=NC=C(N=C12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC1=NC=NC2=NC=C(N=C12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O XQFDFGOXRWRVQY-IBGZPJMESA-N 0.000 description 1
- JVILNXAIIIIIPI-FQEVSTJZSA-N NC1=NN(C=2C1=NC(=CC=2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C Chemical compound NC1=NN(C=2C1=NC(=CC=2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O)C JVILNXAIIIIIPI-FQEVSTJZSA-N 0.000 description 1
- HLOCFFVUBVKJOU-UHFFFAOYSA-N NC=1C(=NC(=CC=1C=O)C)Cl Chemical compound NC=1C(=NC(=CC=1C=O)C)Cl HLOCFFVUBVKJOU-UHFFFAOYSA-N 0.000 description 1
- QNTCSJZXOSFONX-NRFANRHFSA-N NC=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)C(F)F Chemical compound NC=1C2=C(N=CN=1)C=CC(=N2)C=1C=C(C=CC=1)C#C[C@@]1(C(N(CC1)C)=O)C(F)F QNTCSJZXOSFONX-NRFANRHFSA-N 0.000 description 1
- PVFOYAHXMWIDAG-IBGZPJMESA-N NC=1C2=C(N=CN=1)C=NC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=CN=1)C=NC(=N2)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O PVFOYAHXMWIDAG-IBGZPJMESA-N 0.000 description 1
- CXTMHGLFUDUJLE-LJQANCHMSA-N NC=1C2=C(N=CN=1)SC(=N2)C=1C=C(C=CC=1C)C#C[C@@]1(C(N(CC1)C)=O)O Chemical compound NC=1C2=C(N=CN=1)SC(=N2)C=1C=C(C=CC=1C)C#C[C@@]1(C(N(CC1)C)=O)O CXTMHGLFUDUJLE-LJQANCHMSA-N 0.000 description 1
- PXSLPIRGZYESFT-UHFFFAOYSA-N NC=1C=C(C=CC=1)C1=NC=2C(NC=CC=2C=C1)=O Chemical compound NC=1C=C(C=CC=1)C1=NC=2C(NC=CC=2C=C1)=O PXSLPIRGZYESFT-UHFFFAOYSA-N 0.000 description 1
- KEFZOYGUIYWPAG-NRFANRHFSA-N NC=1N=CC=C2C=CC(=NC=12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O Chemical compound NC=1N=CC=C2C=CC(=NC=12)C=1C=C(C=CC=1)C#C[C@]1(C(N(CC1)C)=O)O KEFZOYGUIYWPAG-NRFANRHFSA-N 0.000 description 1
- 108010014632 NF-kappa B kinase Proteins 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- OEBGPJJGERTVPJ-UHFFFAOYSA-N O=C1C(CN(C1=O)CC(F)(F)F)C(=O)OC(C)(C)C Chemical compound O=C1C(CN(C1=O)CC(F)(F)F)C(=O)OC(C)(C)C OEBGPJJGERTVPJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229910019201 POBr3 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102100021996 Staphylococcal nuclease domain-containing protein 1 Human genes 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 102000004393 TNF receptor-associated factor 2 Human genes 0.000 description 1
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 102000000160 Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Human genes 0.000 description 1
- 108010080432 Tumor Necrosis Factor Receptor-Associated Peptides and Proteins Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 101710178300 Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000012391 XPhos Pd G2 Substances 0.000 description 1
- GLPYFDWQKJBUGP-UHFFFAOYSA-N [5-bromo-2-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC(Br)=CC=C1OC(F)(F)F GLPYFDWQKJBUGP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- LDDQLRUQCUTJBB-UHFFFAOYSA-N ammonium fluoride Chemical compound [NH4+].[F-] LDDQLRUQCUTJBB-UHFFFAOYSA-N 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229960003270 belimumab Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AMJQWGIYCROUQF-UHFFFAOYSA-N calcium;methanolate Chemical compound [Ca+2].[O-]C.[O-]C AMJQWGIYCROUQF-UHFFFAOYSA-N 0.000 description 1
- 230000008777 canonical pathway Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000002089 crippling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JRYOZJIRAVZGMV-UHFFFAOYSA-N cyclopropanecarboximidamide;hydron;chloride Chemical compound Cl.NC(=N)C1CC1 JRYOZJIRAVZGMV-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 125000005534 decanoate group Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- ZHNUHDYFZUAESO-MICDWDOJSA-N deuterioformamide Chemical compound [2H]C(N)=O ZHNUHDYFZUAESO-MICDWDOJSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- SLIRLABNGAZSHX-UHFFFAOYSA-N ethyl 2-acetamido-2-cyanoacetate Chemical compound CCOC(=O)C(C#N)NC(C)=O SLIRLABNGAZSHX-UHFFFAOYSA-N 0.000 description 1
- YMBMCMOZIGSBOA-UHFFFAOYSA-N ethyl 2-amino-2-sulfanylideneacetate Chemical compound CCOC(=O)C(N)=S YMBMCMOZIGSBOA-UHFFFAOYSA-N 0.000 description 1
- JTPUHDGFYQNILA-UHFFFAOYSA-N ethyl 4-(3-iodophenyl)-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1=CC=CC(I)=C1 JTPUHDGFYQNILA-UHFFFAOYSA-N 0.000 description 1
- BNFCEIMRFKQNND-UHFFFAOYSA-N ethyl 5-amino-2-chloropyrimidine-4-carboxylate Chemical compound CCOC(=O)C1=NC(Cl)=NC=C1N BNFCEIMRFKQNND-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 description 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000006342 heptafluoro i-propyl group Chemical group FC(F)(F)C(F)(*)C(F)(F)F 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical class OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- PHGCZAQKTOQEQU-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C[C]2C(N)=NC=C=C21 PHGCZAQKTOQEQU-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940033355 lauric acid Drugs 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000011418 maintenance treatment Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- YJEZEMGLLFLMDF-UHFFFAOYSA-N methyl 2-amino-3-methoxybenzoate Chemical compound COC(=O)C1=CC=CC(OC)=C1N YJEZEMGLLFLMDF-UHFFFAOYSA-N 0.000 description 1
- NYKVKANRUGAWAL-UHFFFAOYSA-N methyl 2-amino-5-bromo-3-iodobenzoate Chemical compound COC(=O)C1=CC(Br)=CC(I)=C1N NYKVKANRUGAWAL-UHFFFAOYSA-N 0.000 description 1
- KSZMBXHYSQDICN-UHFFFAOYSA-N methyl 3-amino-2-chloropyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(Cl)=C1N KSZMBXHYSQDICN-UHFFFAOYSA-N 0.000 description 1
- HLNPFWTVHQISEJ-AATRIKPKSA-N methyl 5-[(e)-2-ethoxyethenyl]-2-methylsulfanylpyrimidine-4-carboxylate Chemical compound CCO\C=C\C1=CN=C(SC)N=C1C(=O)OC HLNPFWTVHQISEJ-AATRIKPKSA-N 0.000 description 1
- QRCDYCMZLXMJMY-UHFFFAOYSA-N methyl 5-amino-2-chloro-6-methylpyrimidine-4-carboxylate Chemical compound NC=1C(=NC(=NC=1C)Cl)C(=O)OC QRCDYCMZLXMJMY-UHFFFAOYSA-N 0.000 description 1
- MYZJIEWTRJTWCD-UHFFFAOYSA-N methyl 5-bromo-2-methylsulfanylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=NC(SC)=NC=C1Br MYZJIEWTRJTWCD-UHFFFAOYSA-N 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- ZHNUHDYFZUAESO-AYQNKDEESA-N n,n,1-trideuterioformamide Chemical compound [2H]N([2H])C([2H])=O ZHNUHDYFZUAESO-AYQNKDEESA-N 0.000 description 1
- YWXCPBOLRPNSNZ-UHFFFAOYSA-N n-(1-hydroxypyridin-4-ylidene)hydroxylamine Chemical compound ON=C1C=CN(O)C=C1 YWXCPBOLRPNSNZ-UHFFFAOYSA-N 0.000 description 1
- HWJRIFZDXJKJJN-UHFFFAOYSA-N n-(1h-pyrrolo[2,3-c]pyridin-5-yl)benzamide Chemical compound C=1C=2C=CNC=2C=NC=1NC(=O)C1=CC=CC=C1 HWJRIFZDXJKJJN-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 150000002884 o-xylenes Chemical class 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008008 oral excipient Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940098695 palmitic acid Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000012041 precatalyst Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical compound OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- TZAJKZVNEWSHLN-UHFFFAOYSA-N tert-butyl 3-(2,2,2-trifluoroethylamino)propanoate Chemical compound CC(C)(C)OC(=O)CCNCC(F)(F)F TZAJKZVNEWSHLN-UHFFFAOYSA-N 0.000 description 1
- PHJJRUHXNBAXNI-UHFFFAOYSA-N tert-butyl 4-hydroxy-1-methyl-5-oxo-2H-pyrrole-3-carboxylate Chemical compound CN1CC(C(=O)OC(C)(C)C)=C(O)C1=O PHJJRUHXNBAXNI-UHFFFAOYSA-N 0.000 description 1
- VEERKYYXIIHHQE-UHFFFAOYSA-N tert-butyl N-[2-chloro-4-(2-methylpropanoyl)pyridin-3-yl]carbamate Chemical compound ClC1=NC=CC(=C1NC(OC(C)(C)C)=O)C(C(C)C)=O VEERKYYXIIHHQE-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-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
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- KRRBFUJMQBDDPR-UHFFFAOYSA-N tetrabutylazanium;cyanide Chemical compound N#[C-].CCCC[N+](CCCC)(CCCC)CCCC KRRBFUJMQBDDPR-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000006337 tetrafluoro ethyl 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
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-O tributylphosphanium Chemical compound CCCC[PH+](CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-O 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- 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
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/10—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 carbon chain containing aromatic rings
-
- 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
- C07D403/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- C07D413/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—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
- 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
- C07D417/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962855144P | 2019-05-31 | 2019-05-31 | |
US201962907833P | 2019-09-30 | 2019-09-30 | |
PCT/EP2020/065024 WO2020239999A1 (en) | 2019-05-31 | 2020-05-29 | SMALL MOLECULE INHIBITORS OF NF-kB INDUCING KINASE |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2989387T3 true ES2989387T3 (es) | 2024-11-26 |
Family
ID=71108552
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES20733688T Active ES2989387T3 (es) | 2019-05-31 | 2020-05-29 | Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb |
Country Status (37)
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2989387T3 (es) * | 2019-05-31 | 2024-11-26 | Janssen Pharmaceutica Nv | Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb |
CN114502540A (zh) | 2019-05-31 | 2022-05-13 | 医肯纳肿瘤学公司 | Tead抑制剂和其用途 |
US20250282785A1 (en) * | 2022-05-11 | 2025-09-11 | Janssen Pharmaceutica Nv | Pyrrolidinone derivatives as inhibitors of nf kappa b inducing kinase |
CN119604499A (zh) * | 2022-05-11 | 2025-03-11 | 詹森药业有限公司 | 作为NFκB诱导激酶的抑制剂的吡咯烷酮衍生物 |
US20240279230A1 (en) | 2022-12-22 | 2024-08-22 | Boehringer Ingelheim International Gmbh | Crystalline forms of a her2 inhibitor |
WO2025020886A1 (zh) * | 2023-07-27 | 2025-01-30 | 浙江星浩澎博医药有限公司 | 氮杂喹唑啉环衍生物及其用途 |
WO2025026901A1 (en) | 2023-07-28 | 2025-02-06 | Boehringer Ingelheim International Gmbh | Process for the manufacture of a her2 inhibitor |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9930616D0 (en) | 1999-12-24 | 2000-02-16 | Mathilda & Terence Kennedy Ins | Activation and inhibition of the immune system |
US7132428B2 (en) | 2003-07-03 | 2006-11-07 | Aventis Pharmaceuticals Inc. | Pyrazoloisoquinoline derivative as kinase inhibitors for the treatment of various disorders |
US7592363B2 (en) * | 2004-08-03 | 2009-09-22 | Wyeth | Indazoles |
WO2006053277A2 (en) | 2004-11-12 | 2006-05-18 | Chippac, Inc. | Wire bond interconnection |
CA2728767A1 (en) | 2008-06-26 | 2009-12-30 | Amgen Inc. | Alkynyl alcohols as kinase inhibitors |
US20110183975A1 (en) | 2008-10-07 | 2011-07-28 | Yasuhiro Goto | Novel 6-azaindole aminopyrimidine derivatives having nik inhibitory activity |
EP2686314A1 (en) | 2011-03-16 | 2014-01-22 | F.Hoffmann-La Roche Ag | 6,5-heterocyclic propargylic alcohol compounds and uses therefor |
HK1206024A1 (en) | 2012-02-17 | 2015-12-31 | F. Hoffmann-La Roche Ag | Tricyclic compounds and methods of use therefor |
US8859553B2 (en) | 2012-07-30 | 2014-10-14 | Astar Biotech Llc | Protein kinase inhibitors |
TWI663166B (zh) | 2013-04-24 | 2019-06-21 | 健生藥品公司 | 新化合物 |
MX2016002238A (es) | 2013-08-22 | 2016-05-31 | Hoffmann La Roche | Alcoholes de alquilino y metodos de uso. |
RU2016110021A (ru) * | 2013-08-22 | 2017-09-27 | Ф. Хоффманн-Ля Рош Аг | Алкиниловые спирты и способы их применения |
TWI627173B (zh) | 2013-09-26 | 2018-06-21 | 比利時商健生藥品公司 | 作為NIK抑制劑的新穎3-(1H-吡唑-4-基)-1H-吡咯并[2,3-c]吡啶衍生物 |
TWI704146B (zh) | 2013-09-26 | 2020-09-11 | 比利時商健生藥品公司 | 用作NIK抑制劑之新的1-(4-嘧啶基)-1H-吡唑並[3,2-c]吡啶衍生物 |
JP6603713B2 (ja) | 2014-10-23 | 2019-11-06 | ヤンセン ファーマシューティカ エヌ.ベー. | Nik阻害剤としての新規のチエノピリミジン誘導体 |
EP3209663B1 (en) | 2014-10-23 | 2018-12-12 | Janssen Pharmaceutica N.V. | New pyrazolopyrimidine derivatives as nik inhibitors |
CA2960336C (en) | 2014-10-23 | 2023-03-07 | Janssen Pharmaceutica Nv | Compounds as nik inhibitors |
US9981962B2 (en) | 2014-10-23 | 2018-05-29 | Janssen Pharmaceutica Nv | Pyrazole derivatives as NIK inhibitors |
WO2016135163A1 (en) | 2015-02-25 | 2016-09-01 | F. Hoffmann-La Roche Ag | Alkynyl alcohols and methods of use |
ES2776658T3 (es) | 2016-01-22 | 2020-07-31 | Janssen Pharmaceutica Nv | Nuevos derivados de cianoindolina con sustituyente heteroaromático de 6 miembros como inhibidores de NIK |
WO2017125530A1 (en) | 2016-01-22 | 2017-07-27 | Janssen Pharmaceutica Nv | New substituted cyanoindoline derivatives as nik inhibitors |
EP3478675B1 (en) | 2016-06-30 | 2020-04-22 | Janssen Pharmaceutica NV | Heteroaromatic derivatives as nik inhibitors |
JP6936814B2 (ja) | 2016-06-30 | 2021-09-22 | ヤンセン ファーマシューティカ エヌ.ベー. | Nik阻害剤としてのシアノインドリン誘導体 |
WO2018037058A1 (en) * | 2016-08-24 | 2018-03-01 | F. Hoffmann-La Roche Ag | 2-azabicyclo[3.1.0]hexan-3-one derivatives and methods of use |
CN109641894B (zh) | 2016-08-24 | 2022-09-09 | 豪夫迈·罗氏有限公司 | 2-氮杂双环[3.1.0]己烷-3-酮衍生物及使用方法 |
MX2019014665A (es) | 2017-07-06 | 2020-07-29 | Janssen Pharmaceutica Nv | Nuevos derivados de azaindolina sustituida como inhibidores de nik. |
CN109810110B (zh) * | 2017-11-22 | 2023-01-24 | 中国科学院上海药物研究所 | 一种具有2-氨基嘧啶结构的化合物,其制备方法和用途 |
CN114502540A (zh) | 2019-05-31 | 2022-05-13 | 医肯纳肿瘤学公司 | Tead抑制剂和其用途 |
ES2989387T3 (es) * | 2019-05-31 | 2024-11-26 | Janssen Pharmaceutica Nv | Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb |
SG11202113129UA (en) | 2019-05-31 | 2021-12-30 | Ikena Oncology Inc | Tead inhibitors and uses thereof |
MX2021014115A (es) | 2019-05-31 | 2021-12-10 | Chiesi Farm Spa | Derivados de aminoquinazolina como inhibidores del purinoreceptor 3 de p2x (p2x3). |
CA3139554A1 (en) | 2019-05-31 | 2020-12-03 | Sage Therapeutics, Inc. | Neuroactive steroids and compositions thereof |
JP7559059B2 (ja) | 2019-09-30 | 2024-10-01 | インサイト・コーポレイション | 免疫調節剤としてのピリド[3,2-d]ピリミジン化合物 |
-
2020
- 2020-05-29 ES ES20733688T patent/ES2989387T3/es active Active
- 2020-05-29 CN CN202410972792.2A patent/CN118908957A/zh active Pending
- 2020-05-29 DK DK20733688.4T patent/DK3976597T3/da active
- 2020-05-29 MY MYPI2021007053A patent/MY205653A/en unknown
- 2020-05-29 MX MX2021014679A patent/MX2021014679A/es unknown
- 2020-05-29 CR CR20210587A patent/CR20210587A/es unknown
- 2020-05-29 AU AU2020282005A patent/AU2020282005A1/en active Pending
- 2020-05-29 PH PH1/2021/553011A patent/PH12021553011A1/en unknown
- 2020-05-29 BR BR112021023796A patent/BR112021023796A2/pt unknown
- 2020-05-29 PE PE2021001987A patent/PE20220768A1/es unknown
- 2020-05-29 SM SM20240418T patent/SMT202400418T1/it unknown
- 2020-05-29 PT PT207336884T patent/PT3976597T/pt unknown
- 2020-05-29 CA CA3143350A patent/CA3143350A1/en active Pending
- 2020-05-29 SG SG11202112994WA patent/SG11202112994WA/en unknown
- 2020-05-29 HU HUE20733688A patent/HUE068694T2/hu unknown
- 2020-05-29 PL PL20733688.4T patent/PL3976597T3/pl unknown
- 2020-05-29 KR KR1020217042635A patent/KR20220027871A/ko active Pending
- 2020-05-29 SI SI202030499T patent/SI3976597T1/sl unknown
- 2020-05-29 TW TW109118004A patent/TWI850390B/zh active
- 2020-05-29 UY UY0001038721A patent/UY38721A/es unknown
- 2020-05-29 TW TW113125993A patent/TW202517638A/zh unknown
- 2020-05-29 JP JP2021570919A patent/JP7547387B2/ja active Active
- 2020-05-29 JO JOP/2021/0318A patent/JOP20210318A1/ar unknown
- 2020-05-29 RS RS20241148A patent/RS66105B1/sr unknown
- 2020-05-29 FI FIEP20733688.4T patent/FI3976597T3/fi active
- 2020-05-29 US US16/887,889 patent/US11254673B2/en active Active
- 2020-05-29 MA MA56038A patent/MA56038B1/fr unknown
- 2020-05-29 MD MDE20220374T patent/MD3976597T2/ro unknown
- 2020-05-29 HR HRP20241352TT patent/HRP20241352T1/hr unknown
- 2020-05-29 CN CN202080057418.XA patent/CN114222737B/zh active Active
- 2020-05-29 EP EP20733688.4A patent/EP3976597B1/en active Active
- 2020-05-29 LT LTEPPCT/EP2020/065024T patent/LT3976597T/lt unknown
- 2020-05-29 EP EP24188073.1A patent/EP4467199A3/en active Pending
- 2020-05-29 WO PCT/EP2020/065024 patent/WO2020239999A1/en active IP Right Grant
-
2021
- 2021-11-25 CL CL2021003142A patent/CL2021003142A1/es unknown
- 2021-11-25 IL IL288387A patent/IL288387B1/en unknown
- 2021-11-26 DO DO2021000244A patent/DOP2021000244A/es unknown
- 2021-11-30 SA SA521430960A patent/SA521430960B1/ar unknown
- 2021-12-13 US US17/549,057 patent/US11827634B2/en active Active
- 2021-12-27 CO CONC2021/0017838A patent/CO2021017838A2/es unknown
- 2021-12-28 EC ECSENADI202193623A patent/ECSP21093623A/es unknown
-
2023
- 2023-09-27 US US18/475,499 patent/US20240199605A1/en active Pending
-
2024
- 2024-08-28 JP JP2024146717A patent/JP2024167319A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2989387T3 (es) | Pequeñas moléculas inhibidoras de la quinasa inductora de nf-kb | |
ES2908412T3 (es) | Derivados de piperidin-4-IL azetidina como inhibidores de JAK1 | |
US8962596B2 (en) | 5,7-substituted-imidazo[1,2-C]pyrimidines as inhibitors of JAK kinases | |
KR102516711B1 (ko) | P2x7 조절제 | |
ES2654288T3 (es) | Moduladores de P2X7 | |
BR112015032330B1 (pt) | carboxamidas primárias como inibidores de bkt | |
TW201326173A (zh) | 5,7-經取代之-咪唑并[1,2-c]嘧啶 | |
JP2011529920A (ja) | ピリミジン化合物、組成物及び使用方法 | |
EA032839B1 (ru) | Конденсированные пентациклические производные имидазола | |
BR112020012651A2 (pt) | compostos derivados de aril-bipiridina amina como inibidores da fosfatidilinositol fosfato quinase, composição farmacêutica compreendendo os mesmos e usos terapêuticos dos ditos compostos | |
JP7413368B2 (ja) | モノアシルグリセロールリパーゼ調節因子 | |
CA2984307A1 (en) | Imidazopyrazines and pyrazolopyrimidines and their use as ampa receptor modulators | |
JP2023536920A (ja) | 塩誘導性キナーゼ阻害剤 | |
WO2020223590A1 (en) | Modulators of trex1 | |
WO2023283369A1 (en) | Modulators of protein kinases | |
EA045720B1 (ru) | НИЗКОМОЛЕКУЛЯРНЫЕ ИНГИБИТОРЫ NF-κB-ИНДУЦИРУЮЩЕЙ КИНАЗЫ | |
HK40071178A (en) | Small molecule inhibitors of nf-kb inducing kinase | |
HK40071178B (en) | Small molecule inhibitors of nf-kb inducing kinase | |
JP2025516597A (ja) | Nfカッパb誘導性キナーゼの阻害剤としてのピロリジノン誘導体 | |
TW202527931A (zh) | 視紫質的藥理校正劑及其用途 | |
TW202513561A (zh) | 治療發炎性疾病之方法 |