SK125999A3 - Pyrrolo[2,3d]pyrimidines and their use as tyrosine kinase inhibitors - Google Patents

Info

Publication number

SK125999A3

SK125999A3 SK1259-99A SK125999A SK125999A3 SK 125999 A3 SK125999 A3 SK 125999A3 SK 125999 A SK125999 A SK 125999A SK 125999 A3 SK125999 A3 SK 125999A3

Authority

SK

Slovakia

Prior art keywords

alloy

phenyl

chromium

pyrrolo

pyrimidin

Prior art date

1997-03-19

Links

• Espacenet
• Global Dossier
• Discuss

• 229940121358 tyrosine kinase inhibitor Drugs 0.000 title description 2
• 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 2
• 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 title 1
• -1 2-phenyl-1,3-dioxan-5-yl Chemical group 0.000 claims abstract description 241
• 150000001875 compounds Chemical class 0.000 claims abstract description 177
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 122
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 88
• 238000000034 method Methods 0.000 claims abstract description 56
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 50
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 37
• 150000003839 salts Chemical class 0.000 claims abstract description 26
• 239000001257 hydrogen Substances 0.000 claims abstract description 22
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 20
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
• 230000008569 process Effects 0.000 claims abstract description 15
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 14
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims abstract description 13
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 10
• 230000002062 proliferating effect Effects 0.000 claims abstract description 10
• 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 9
• 125000005544 phthalimido group Chemical group 0.000 claims abstract description 7
• 241000124008 Mammalia Species 0.000 claims abstract description 5
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
• 239000000203 mixture Substances 0.000 claims description 187
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 52
• 229910052736 halogen Inorganic materials 0.000 claims description 39
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
• 239000000463 material Substances 0.000 claims description 34
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 33
• 150000002367 halogens Chemical class 0.000 claims description 33
• 239000011159 matrix material Substances 0.000 claims description 33
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 32
• 239000012071 phase Substances 0.000 claims description 30
• 239000002245 particle Substances 0.000 claims description 29
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 29
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
• 239000000843 powder Substances 0.000 claims description 27
• 230000002829 reductive effect Effects 0.000 claims description 27
• 239000006185 dispersion Substances 0.000 claims description 26
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 26
• 239000000047 product Substances 0.000 claims description 24
• 201000010099 disease Diseases 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• 239000010410 layer Substances 0.000 claims description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 21
• 238000004519 manufacturing process Methods 0.000 claims description 21
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 20
• 238000006243 chemical reaction Methods 0.000 claims description 19
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 17
• 238000011282 treatment Methods 0.000 claims description 16
• 229910021529 ammonia Inorganic materials 0.000 claims description 15
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• 150000002431 hydrogen Chemical class 0.000 claims description 11
• 238000002360 preparation method Methods 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 9
• 238000001816 cooling Methods 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 8
• 238000012360 testing method Methods 0.000 claims description 7
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
• NFSWHYRUVWRUDN-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NFSWHYRUVWRUDN-UHFFFAOYSA-N 0.000 claims description 6
• 241000282414 Homo sapiens Species 0.000 claims description 6
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 6
• 239000003054 catalyst Substances 0.000 claims description 6
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
• 239000008187 granular material Substances 0.000 claims description 6
• 208000026278 immune system disease Diseases 0.000 claims description 6
• 238000002844 melting Methods 0.000 claims description 6
• 230000008018 melting Effects 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 4
• 239000004146 Propane-1,2-diol Substances 0.000 claims description 4
• 125000005605 benzo group Chemical group 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 238000010438 heat treatment Methods 0.000 claims description 4
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 238000002156 mixing Methods 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 230000001613 neoplastic effect Effects 0.000 claims description 4
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 229920006395 saturated elastomer Polymers 0.000 claims description 4
• 238000003786 synthesis reaction Methods 0.000 claims description 4
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 230000015556 catabolic process Effects 0.000 claims description 3
• 239000007789 gas Substances 0.000 claims description 3
• 238000012423 maintenance Methods 0.000 claims description 3
• LYBNLOMPRHYDRF-UHFFFAOYSA-N 2-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1O LYBNLOMPRHYDRF-UHFFFAOYSA-N 0.000 claims description 2
• PIJBBYHMSXEZMC-UHFFFAOYSA-N 5-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-2-nitrobenzoic acid Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1 PIJBBYHMSXEZMC-UHFFFAOYSA-N 0.000 claims description 2
• SMKWVLYWUQBZKW-UHFFFAOYSA-N 5-[4-(benzenesulfinyl)phenyl]-7-tert-butylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1S(=O)C1=CC=CC=C1 SMKWVLYWUQBZKW-UHFFFAOYSA-N 0.000 claims description 2
• PAHKLGUKLSFIBQ-UHFFFAOYSA-N 7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C1=CC=CC=C1OC1=CC=CC=C1 PAHKLGUKLSFIBQ-UHFFFAOYSA-N 0.000 claims description 2
• ISMWZGJUONENAM-UHFFFAOYSA-N 7-tert-butyl-5-(4-phenylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1C1=CC=CC=C1 ISMWZGJUONENAM-UHFFFAOYSA-N 0.000 claims description 2
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
• 150000003863 ammonium salts Chemical class 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000005543 phthalimide group Chemical group 0.000 claims description 2
• 239000002244 precipitate Substances 0.000 claims description 2
• 239000003755 preservative agent Substances 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
• 229910045601 alloy Inorganic materials 0.000 claims 126
• 239000000956 alloy Substances 0.000 claims 126
• 239000011651 chromium Substances 0.000 claims 119
• 229910052804 chromium Inorganic materials 0.000 claims 55
• VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 53
• WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims 39
• 230000003647 oxidation Effects 0.000 claims 38
• 238000007254 oxidation reaction Methods 0.000 claims 38
• 229910000423 chromium oxide Inorganic materials 0.000 claims 34
• 229910052751 metal Inorganic materials 0.000 claims 24
• 239000002184 metal Substances 0.000 claims 24
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims 21
• 229910052721 tungsten Inorganic materials 0.000 claims 19
• 238000005260 corrosion Methods 0.000 claims 18
• 230000007797 corrosion Effects 0.000 claims 18
• 239000011521 glass Substances 0.000 claims 18
• WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims 17
• 229910052750 molybdenum Inorganic materials 0.000 claims 16
• 239000002243 precursor Substances 0.000 claims 16
• 239000010937 tungsten Substances 0.000 claims 16
• ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims 15
• 230000000052 comparative effect Effects 0.000 claims 14
• 239000011733 molybdenum Substances 0.000 claims 14
• 239000006060 molten glass Substances 0.000 claims 13
• 238000005245 sintering Methods 0.000 claims 11
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims 10
• 230000001590 oxidative effect Effects 0.000 claims 10
• VNNRSPGTAMTISX-UHFFFAOYSA-N chromium nickel Chemical compound [Cr].[Ni] VNNRSPGTAMTISX-UHFFFAOYSA-N 0.000 claims 8
• 229910052742 iron Inorganic materials 0.000 claims 8
• 238000001757 thermogravimetry curve Methods 0.000 claims 8
• 229910052759 nickel Inorganic materials 0.000 claims 7
• 238000002161 passivation Methods 0.000 claims 7
• 239000011241 protective layer Substances 0.000 claims 7
• 239000003870 refractory metal Substances 0.000 claims 7
• UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims 6
• 238000000137 annealing Methods 0.000 claims 6
• 239000000835 fiber Substances 0.000 claims 6
• 229910018487 Ni—Cr Inorganic materials 0.000 claims 5
• 229910052786 argon Inorganic materials 0.000 claims 5
• 229940117975 chromium trioxide Drugs 0.000 claims 5
• GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims 5
• 229910017052 cobalt Inorganic materials 0.000 claims 5
• 239000010941 cobalt Substances 0.000 claims 5
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims 5
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 5
• 229910000753 refractory alloy Inorganic materials 0.000 claims 5
• 230000035882 stress Effects 0.000 claims 5
• 239000002344 surface layer Substances 0.000 claims 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 4
• 230000003628 erosive effect Effects 0.000 claims 4
• 238000007731 hot pressing Methods 0.000 claims 4
• 239000001301 oxygen Substances 0.000 claims 4
• 229910052763 palladium Inorganic materials 0.000 claims 4
• 230000009471 action Effects 0.000 claims 3
• 238000005516 engineering process Methods 0.000 claims 3
• 239000003365 glass fiber Substances 0.000 claims 3
• 239000011491 glass wool Substances 0.000 claims 3
• 239000012535 impurity Substances 0.000 claims 3
• 238000011065 in-situ storage Methods 0.000 claims 3
• 239000011261 inert gas Substances 0.000 claims 3
• 238000005551 mechanical alloying Methods 0.000 claims 3
• 150000002736 metal compounds Chemical class 0.000 claims 3
• 229910052758 niobium Inorganic materials 0.000 claims 3
• 239000010955 niobium Substances 0.000 claims 3
• GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 claims 3
• 238000003825 pressing Methods 0.000 claims 3
• 229910052715 tantalum Inorganic materials 0.000 claims 3
• GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims 3
• 230000004584 weight gain Effects 0.000 claims 3
• 235000019786 weight gain Nutrition 0.000 claims 3
• ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 claims 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
• 229910052684 Cerium Inorganic materials 0.000 claims 2
• 229910000684 Cobalt-chrome Inorganic materials 0.000 claims 2
• 229910052776 Thorium Inorganic materials 0.000 claims 2
• QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims 2
• WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 claims 2
• ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 claims 2
• AXTNPHLCOKUMDY-UHFFFAOYSA-N chromium cobalt Chemical compound [Co][Cr][Co] AXTNPHLCOKUMDY-UHFFFAOYSA-N 0.000 claims 2
• SZMZREIADCOWQA-UHFFFAOYSA-N chromium cobalt nickel Chemical compound [Cr].[Co].[Ni] SZMZREIADCOWQA-UHFFFAOYSA-N 0.000 claims 2
• UPHIPHFJVNKLMR-UHFFFAOYSA-N chromium iron Chemical compound [Cr].[Fe] UPHIPHFJVNKLMR-UHFFFAOYSA-N 0.000 claims 2
• OYSYRRRAJPTBHI-UHFFFAOYSA-N chromium molybdenum tungsten Chemical compound [Cr][W][Mo] OYSYRRRAJPTBHI-UHFFFAOYSA-N 0.000 claims 2
• 239000011248 coating agent Substances 0.000 claims 2
• 238000000576 coating method Methods 0.000 claims 2
• 239000010952 cobalt-chrome Substances 0.000 claims 2
• 238000007596 consolidation process Methods 0.000 claims 2
• 238000009792 diffusion process Methods 0.000 claims 2
• 238000009826 distribution Methods 0.000 claims 2
• 238000005242 forging Methods 0.000 claims 2
• 239000010439 graphite Substances 0.000 claims 2
• 229910002804 graphite Inorganic materials 0.000 claims 2
• 238000000227 grinding Methods 0.000 claims 2
• 229910052735 hafnium Inorganic materials 0.000 claims 2
• VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 claims 2
• 230000006872 improvement Effects 0.000 claims 2
• 229910052746 lanthanum Inorganic materials 0.000 claims 2
• FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims 2
• 150000002739 metals Chemical class 0.000 claims 2
• 239000004570 mortar (masonry) Substances 0.000 claims 2
• 229910000623 nickel–chromium alloy Inorganic materials 0.000 claims 2
• 238000005121 nitriding Methods 0.000 claims 2
• 229910052697 platinum Inorganic materials 0.000 claims 2
• 230000002787 reinforcement Effects 0.000 claims 2
• 239000000523 sample Substances 0.000 claims 2
• 239000006104 solid solution Substances 0.000 claims 2
• 239000000126 substance Substances 0.000 claims 2
• 239000004753 textile Substances 0.000 claims 2
• 238000009827 uniform distribution Methods 0.000 claims 2
• 230000004580 weight loss Effects 0.000 claims 2
• 238000003466 welding Methods 0.000 claims 2
• 229910052726 zirconium Inorganic materials 0.000 claims 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
• 229910000714 At alloy Inorganic materials 0.000 claims 1
• HJJXVPUOMJYVPN-UHFFFAOYSA-N C1(CCCC1)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2.C(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=CC=C1 Chemical compound C1(CCCC1)N1C=C(C2=C1N=CN=C2N)C2=CC=C(C=C2)OC2=CC=CC=C2.C(C)(C)N2C=C(C1=C2N=CN=C1N)C1=CC=C(C=C1)OC1=CC=CC=C1 HJJXVPUOMJYVPN-UHFFFAOYSA-N 0.000 claims 1
• 229910000531 Co alloy Inorganic materials 0.000 claims 1
• OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 claims 1
• 229910000990 Ni alloy Inorganic materials 0.000 claims 1
• 229910000831 Steel Inorganic materials 0.000 claims 1
• QXZUUHYBWMWJHK-UHFFFAOYSA-N [Co].[Ni] Chemical compound [Co].[Ni] QXZUUHYBWMWJHK-UHFFFAOYSA-N 0.000 claims 1
• WBWJXRJARNTNBL-UHFFFAOYSA-N [Fe].[Cr].[Co] Chemical compound [Fe].[Cr].[Co] WBWJXRJARNTNBL-UHFFFAOYSA-N 0.000 claims 1
• RMXTYBQNQCQHEU-UHFFFAOYSA-N ac1lawpn Chemical compound [Cr]#[Cr] RMXTYBQNQCQHEU-UHFFFAOYSA-N 0.000 claims 1
• 125000002252 acyl group Chemical group 0.000 claims 1
• 238000005275 alloying Methods 0.000 claims 1
• 238000004873 anchoring Methods 0.000 claims 1
• 239000011324 bead Substances 0.000 claims 1
• 230000009286 beneficial effect Effects 0.000 claims 1
• 238000005119 centrifugation Methods 0.000 claims 1
• 239000000919 ceramic Substances 0.000 claims 1
• BIJOYKCOMBZXAE-UHFFFAOYSA-N chromium iron nickel Chemical compound [Cr].[Fe].[Ni] BIJOYKCOMBZXAE-UHFFFAOYSA-N 0.000 claims 1
• VNTLIPZTSJSULJ-UHFFFAOYSA-N chromium molybdenum Chemical compound [Cr].[Mo] VNTLIPZTSJSULJ-UHFFFAOYSA-N 0.000 claims 1
• NVIVJPRCKQTWLY-UHFFFAOYSA-N cobalt nickel Chemical compound [Co][Ni][Co] NVIVJPRCKQTWLY-UHFFFAOYSA-N 0.000 claims 1
• XTUHPOUJWWTMNC-UHFFFAOYSA-N cobalt(2+);dioxido(dioxo)chromium Chemical class [Co+2].[O-][Cr]([O-])(=O)=O XTUHPOUJWWTMNC-UHFFFAOYSA-N 0.000 claims 1
• 230000006835 compression Effects 0.000 claims 1
• 238000007906 compression Methods 0.000 claims 1
• 239000005356 container glass Substances 0.000 claims 1
• 238000011109 contamination Methods 0.000 claims 1
• 238000007796 conventional method Methods 0.000 claims 1
• 230000007423 decrease Effects 0.000 claims 1
• 238000006731 degradation reaction Methods 0.000 claims 1
• 230000001934 delay Effects 0.000 claims 1
• 238000005485 electric heating Methods 0.000 claims 1
• 238000000840 electrochemical analysis Methods 0.000 claims 1
• 238000002848 electrochemical method Methods 0.000 claims 1
• 238000001125 extrusion Methods 0.000 claims 1
• 239000010419 fine particle Substances 0.000 claims 1
• 239000008240 homogeneous mixture Substances 0.000 claims 1
• 238000009776 industrial production Methods 0.000 claims 1
• 238000009413 insulation Methods 0.000 claims 1
• 229910000765 intermetallic Inorganic materials 0.000 claims 1
• 238000000462 isostatic pressing Methods 0.000 claims 1
• 238000005297 material degradation process Methods 0.000 claims 1
• 238000005259 measurement Methods 0.000 claims 1
• 229910001092 metal group alloy Inorganic materials 0.000 claims 1
• 229910044991 metal oxide Inorganic materials 0.000 claims 1
• 150000004706 metal oxides Chemical class 0.000 claims 1
• 238000004452 microanalysis Methods 0.000 claims 1
• 239000002557 mineral fiber Substances 0.000 claims 1
• 229910001120 nichrome Inorganic materials 0.000 claims 1
• 229910000480 nickel oxide Inorganic materials 0.000 claims 1
• 230000003287 optical effect Effects 0.000 claims 1
• 238000013021 overheating Methods 0.000 claims 1
• 229910001175 oxide dispersion-strengthened alloy Inorganic materials 0.000 claims 1
• SIWVEOZUMHYXCS-UHFFFAOYSA-N oxo(oxoyttriooxy)yttrium Chemical compound O=[Y]O[Y]=O SIWVEOZUMHYXCS-UHFFFAOYSA-N 0.000 claims 1
• GNRSAWUEBMWBQH-UHFFFAOYSA-N oxonickel Chemical compound [Ni]=O GNRSAWUEBMWBQH-UHFFFAOYSA-N 0.000 claims 1
• 150000002927 oxygen compounds Chemical class 0.000 claims 1
• 238000010587 phase diagram Methods 0.000 claims 1
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 238000007780 powder milling Methods 0.000 claims 1
• 230000009257 reactivity Effects 0.000 claims 1
• 238000006479 redox reaction Methods 0.000 claims 1
• 239000011819 refractory material Substances 0.000 claims 1
• 238000005096 rolling process Methods 0.000 claims 1
• 230000035945 sensitivity Effects 0.000 claims 1
• 230000035939 shock Effects 0.000 claims 1
• 239000002893 slag Substances 0.000 claims 1
• 241000894007 species Species 0.000 claims 1
• 239000010959 steel Substances 0.000 claims 1
• 229910000601 superalloy Inorganic materials 0.000 claims 1
• 230000008646 thermal stress Effects 0.000 claims 1
• 238000003826 uniaxial pressing Methods 0.000 claims 1
• 210000002268 wool Anatomy 0.000 claims 1
• 229910052727 yttrium Inorganic materials 0.000 claims 1
• VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims 1
• RUDFQVOCFDJEEF-UHFFFAOYSA-N yttrium(III) oxide Inorganic materials [O-2].[O-2].[O-2].[Y+3].[Y+3] RUDFQVOCFDJEEF-UHFFFAOYSA-N 0.000 claims 1
• 210000000987 immune system Anatomy 0.000 abstract description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 2
• 125000001475 halogen functional group Chemical group 0.000 abstract 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
• 208000037765 diseases and disorders Diseases 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 172
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• 239000000243 solution Substances 0.000 description 52
• 239000007787 solid Substances 0.000 description 47
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 238000003756 stirring Methods 0.000 description 26
• 239000000377 silicon dioxide Substances 0.000 description 25
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
• 238000003818 flash chromatography Methods 0.000 description 22
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 238000010992 reflux Methods 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• 239000011928 denatured alcohol Substances 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 239000003826 tablet Substances 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 238000001819 mass spectrum Methods 0.000 description 11
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 11
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 10
• 241000699670 Mus sp. Species 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 10
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 210000001744 T-lymphocyte Anatomy 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• 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 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 230000006044 T cell activation Effects 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 235000010446 mineral oil Nutrition 0.000 description 6
• 150000002825 nitriles Chemical class 0.000 description 6
• 235000018102 proteins Nutrition 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
• CBWBJFJMNBPWAL-UHFFFAOYSA-N 4-chloro-5-iodo-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C(I)=CN2 CBWBJFJMNBPWAL-UHFFFAOYSA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 102000000588 Interleukin-2 Human genes 0.000 description 5
• 108010002350 Interleukin-2 Proteins 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 239000002024 ethyl acetate extract Substances 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• RAXTYMXDSNWNJS-UHFFFAOYSA-N 2-bromo-1-(4-phenoxyphenyl)ethanone Chemical compound C1=CC(C(=O)CBr)=CC=C1OC1=CC=CC=C1 RAXTYMXDSNWNJS-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
• PJIYFOYIHIDOJN-UHFFFAOYSA-N 4-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclopent-2-en-1-ol Chemical compound C1=2C(N)=NC=NC=2N(C2C=CC(O)C2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 PJIYFOYIHIDOJN-UHFFFAOYSA-N 0.000 description 4
• KJHYDYATVCGFKG-UHFFFAOYSA-N 4-chloro-5-iodo-7-propan-2-ylpyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2N(C(C)C)C=C(I)C2=C1Cl KJHYDYATVCGFKG-UHFFFAOYSA-N 0.000 description 4
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
• 208000009386 Experimental Arthritis Diseases 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
• 239000000427 antigen Substances 0.000 description 4
• 108091007433 antigens Proteins 0.000 description 4
• 102000036639 antigens Human genes 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 238000002425 crystallisation Methods 0.000 description 4
• 230000008025 crystallization Effects 0.000 description 4
• 239000012362 glacial acetic acid Substances 0.000 description 4
• 230000003053 immunization Effects 0.000 description 4
• 238000002649 immunization Methods 0.000 description 4
• 239000006201 parenteral dosage form Substances 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 229960004063 propylene glycol Drugs 0.000 description 4
• 235000013772 propylene glycol Nutrition 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
• OZSXUVWJCWELFF-UHFFFAOYSA-N 4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenol Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C1=CC=C(O)C=C1 OZSXUVWJCWELFF-UHFFFAOYSA-N 0.000 description 3
• VVJNBQCLBXPLKC-UHFFFAOYSA-N 4-(4-chloro-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)aniline Chemical compound C12=C(Cl)N=CN=C2N(C(C)C)C=C1C1=CC=C(N)C=C1 VVJNBQCLBXPLKC-UHFFFAOYSA-N 0.000 description 3
• SZBOWPMFRHBAES-UHFFFAOYSA-N 4-chloro-7-cyclopentyl-5-iodopyrrolo[2,3-d]pyrimidine Chemical compound C1=C(I)C=2C(Cl)=NC=NC=2N1C1CCCC1 SZBOWPMFRHBAES-UHFFFAOYSA-N 0.000 description 3
• CIHPWICLKKWTAY-UHFFFAOYSA-N 7-tert-butyl-5-(4-phenylsulfanylphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1SC1=CC=CC=C1 CIHPWICLKKWTAY-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• 239000005725 8-Hydroxyquinoline Substances 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• 208000023275 Autoimmune disease Diseases 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
• 238000002965 ELISA Methods 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 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
• 108010074328 Interferon-gamma Proteins 0.000 description 3
• 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 3
• 241001465754 Metazoa Species 0.000 description 3
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 235000001014 amino acid Nutrition 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 235000011114 ammonium hydroxide Nutrition 0.000 description 3
• 125000003118 aryl group Chemical group 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 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 3
• 230000004663 cell proliferation Effects 0.000 description 3
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 201000002491 encephalomyelitis Diseases 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 229960003540 oxyquinoline Drugs 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[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.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• WIKBZUXHNPONPP-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-iodo-2-(trifluoromethyl)propane Chemical compound FC(F)(F)C(I)(C(F)(F)F)C(F)(F)F WIKBZUXHNPONPP-UHFFFAOYSA-N 0.000 description 2
• DJNIFZYQFLFGDT-UHFFFAOYSA-N 1-(4-phenoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OC1=CC=CC=C1 DJNIFZYQFLFGDT-UHFFFAOYSA-N 0.000 description 2
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
• SUGIXUOLQCWZSX-UHFFFAOYSA-N 2-amino-1-tert-butyl-4-(4-phenoxyphenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 SUGIXUOLQCWZSX-UHFFFAOYSA-N 0.000 description 2
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
• GKNORMADYXCWRJ-UHFFFAOYSA-N 4-[4-(4-amino-7h-pyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=C(O)C=C1 GKNORMADYXCWRJ-UHFFFAOYSA-N 0.000 description 2
• DLJBKUOXIIRHOS-UHFFFAOYSA-N 4-chloro-5-(4-methoxyphenyl)-7-propan-2-ylpyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=CN(C(C)C)C2=NC=NC(Cl)=C12 DLJBKUOXIIRHOS-UHFFFAOYSA-N 0.000 description 2
• MDEAPLPJVDTMSN-UHFFFAOYSA-N 4-chloro-5-(4-nitrophenyl)-7-propan-2-ylpyrrolo[2,3-d]pyrimidine Chemical compound C12=C(Cl)N=CN=C2N(C(C)C)C=C1C1=CC=C([N+]([O-])=O)C=C1 MDEAPLPJVDTMSN-UHFFFAOYSA-N 0.000 description 2
• KYDZEZNYRFJCSA-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 KYDZEZNYRFJCSA-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• PIONBRMJOSUEHB-UHFFFAOYSA-N 5-(4-aminophenyl)-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C1=CC=C(N)C=C1 PIONBRMJOSUEHB-UHFFFAOYSA-N 0.000 description 2
• KTGZCXGZOLDVSP-UHFFFAOYSA-N 5-(4-methoxyphenyl)-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1C1=CN(C(C)C)C2=NC=NC(N)=C12 KTGZCXGZOLDVSP-UHFFFAOYSA-N 0.000 description 2
• ITJWOPPSOKMWCK-UHFFFAOYSA-N 5-[4-(2-aminophenoxy)phenyl]-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1N ITJWOPPSOKMWCK-UHFFFAOYSA-N 0.000 description 2
• PWEMILVNKQAISL-UHFFFAOYSA-N 5-[4-(2-nitrophenoxy)phenyl]-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1[N+]([O-])=O PWEMILVNKQAISL-UHFFFAOYSA-N 0.000 description 2
• QJSJCFHSACXKCC-UHFFFAOYSA-N 5-[4-(4-aminophenoxy)phenyl]-7-tert-butylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C(N)C=C1 QJSJCFHSACXKCC-UHFFFAOYSA-N 0.000 description 2
• KNDIBTBKZBMNBL-UHFFFAOYSA-N 6-chloro-7-cyclopentyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound ClC1=C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C=2C(N)=NC=NC=2N1C1CCCC1 KNDIBTBKZBMNBL-UHFFFAOYSA-N 0.000 description 2
• PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical class NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
• YXEKEVOINGFDHV-UHFFFAOYSA-N 7-tert-butyl-5-(4-iodophenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C1=CC=C(I)C=C1 YXEKEVOINGFDHV-UHFFFAOYSA-N 0.000 description 2
• MYSJNRWPLKEUQT-UHFFFAOYSA-N 7-tert-butyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 MYSJNRWPLKEUQT-UHFFFAOYSA-N 0.000 description 2
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000933320 Homo sapiens Breakpoint cluster region protein Proteins 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 102100037850 Interferon gamma Human genes 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• 101150093908 PDGFRB gene Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 108700020978 Proto-Oncogene Proteins 0.000 description 2
• 102000052575 Proto-Oncogene Human genes 0.000 description 2
• FMETVQKSDIOGPX-UHFFFAOYSA-N RK-24466 Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 FMETVQKSDIOGPX-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
• 238000005576 amination reaction Methods 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 230000003305 autocrine Effects 0.000 description 2
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 2
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 238000009505 enteric coating Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 238000001030 gas--liquid chromatography Methods 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 208000024908 graft versus host disease Diseases 0.000 description 2
• 239000003102 growth factor Substances 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• DLDIDQIZPBIVNQ-UHFFFAOYSA-N hydron;2-methylpropan-2-amine;chloride Chemical compound Cl.CC(C)(C)N DLDIDQIZPBIVNQ-UHFFFAOYSA-N 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 239000002198 insoluble material Substances 0.000 description 2
• 230000004073 interleukin-2 production Effects 0.000 description 2
• 125000002346 iodo group Chemical group I* 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000001165 lymph node Anatomy 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• JTUVMRUPITZIEE-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-hydroxyphenyl]-4-chlorobenzamide Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C(C=C1O)=CC=C1NC(=O)C1=CC=C(Cl)C=C1 JTUVMRUPITZIEE-UHFFFAOYSA-N 0.000 description 2
• CQVAFFLGWYZWPH-UHFFFAOYSA-N n-[4-(4-chloro-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]benzenesulfonamide Chemical compound C12=C(Cl)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=CC=C1 CQVAFFLGWYZWPH-UHFFFAOYSA-N 0.000 description 2
• NTBAONGQXIYCBE-UHFFFAOYSA-N n-[4-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 NTBAONGQXIYCBE-UHFFFAOYSA-N 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 239000012285 osmium tetroxide Substances 0.000 description 2
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
• 150000003891 oxalate salts Chemical class 0.000 description 2
• NFHFRUOZVGFOOS-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.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 2
• 235000019271 petrolatum Nutrition 0.000 description 2
• 239000003208 petroleum Substances 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-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
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 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 2
• 239000012485 toluene extract Substances 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 239000012049 topical pharmaceutical composition Substances 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 238000010626 work up procedure Methods 0.000 description 2
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• KFXUHRXGLWUOJT-UHFFFAOYSA-N (4-phenoxyphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1OC1=CC=CC=C1 KFXUHRXGLWUOJT-UHFFFAOYSA-N 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
• HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 1
• UGRMITBWUVWUEB-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-3-methylbenzene Chemical group CC1=CC=CC([O])=C1 UGRMITBWUVWUEB-UHFFFAOYSA-N 0.000 description 1
• HZRAUMRZKGXMEL-UHFFFAOYSA-N 1-[4-(4-methoxyphenoxy)phenyl]-3,3-dimethylbutan-1-one;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1OC1=CC=C(C(=O)CC(C)(C)C)C=C1 HZRAUMRZKGXMEL-UHFFFAOYSA-N 0.000 description 1
• ICXPZMQQZWKKMN-UHFFFAOYSA-N 1-[4-(4-methoxyphenoxy)phenyl]ethanone Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C(C)=O)C=C1 ICXPZMQQZWKKMN-UHFFFAOYSA-N 0.000 description 1
• RRWFUWRLNIZICP-UHFFFAOYSA-N 1-bromo-2-phenoxybenzene Chemical compound BrC1=CC=CC=C1OC1=CC=CC=C1 RRWFUWRLNIZICP-UHFFFAOYSA-N 0.000 description 1
• AHDAKFFMKLQPTD-UHFFFAOYSA-N 1-bromo-3-phenoxybenzene Chemical compound BrC1=CC=CC(OC=2C=CC=CC=2)=C1 AHDAKFFMKLQPTD-UHFFFAOYSA-N 0.000 description 1
• PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
• XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 1
• LZDMQFOLXJUDLT-UHFFFAOYSA-N 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-(3-chlorophenoxy)benzamide Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)C(N)=O)=CC=C1OC1=CC=CC(Cl)=C1 LZDMQFOLXJUDLT-UHFFFAOYSA-N 0.000 description 1
• FXJMGPTUCHENMZ-UHFFFAOYSA-N 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-(3-chlorophenoxy)phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)O)=CC=C1OC1=CC=CC(Cl)=C1 FXJMGPTUCHENMZ-UHFFFAOYSA-N 0.000 description 1
• PCIKKNSDIXLMOX-UHFFFAOYSA-N 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-phenoxybenzamide Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)C(N)=O)=CC=C1OC1=CC=CC=C1 PCIKKNSDIXLMOX-UHFFFAOYSA-N 0.000 description 1
• RRLZPBGVTUNYLG-UHFFFAOYSA-N 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-phenoxyphenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)O)=CC=C1OC1=CC=CC=C1 RRLZPBGVTUNYLG-UHFFFAOYSA-N 0.000 description 1
• QHBJFDHGXHZZSG-UHFFFAOYSA-N 2-(tert-butylamino)-1-(4-iodophenyl)ethanone;hydrochloride Chemical compound Cl.CC(C)(C)NCC(=O)C1=CC=C(I)C=C1 QHBJFDHGXHZZSG-UHFFFAOYSA-N 0.000 description 1
• ZHKCKKMMBOHRCY-UHFFFAOYSA-N 2-(tert-butylamino)-1-(4-phenoxyphenyl)ethanone;hydrochloride Chemical compound Cl.C1=CC(C(=O)CNC(C)(C)C)=CC=C1OC1=CC=CC=C1 ZHKCKKMMBOHRCY-UHFFFAOYSA-N 0.000 description 1
• HXEJQDISGVLYOE-UHFFFAOYSA-N 2-(tert-butylamino)-1-phenylethanone hydrochloride Chemical compound Cl.C(C)(C)(C)NCC(=O)C1=CC=CC=C1 HXEJQDISGVLYOE-UHFFFAOYSA-N 0.000 description 1
• ZCBPGURKZDCEFP-UHFFFAOYSA-N 2-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-5-nitrobenzoic acid Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1C(O)=O ZCBPGURKZDCEFP-UHFFFAOYSA-N 0.000 description 1
• MNBVQSKOALBMNJ-UHFFFAOYSA-N 2-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1O MNBVQSKOALBMNJ-UHFFFAOYSA-N 0.000 description 1
• XBTDIGWGOZVBHQ-UHFFFAOYSA-N 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentan-1-ol Chemical compound C1=2C(N)=NC=NC=2N(C2C(CCC2)O)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XBTDIGWGOZVBHQ-UHFFFAOYSA-N 0.000 description 1
• AFGOFEFLRMONQO-UHFFFAOYSA-N 2-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]ethanol Chemical compound C1=2C(N)=NC=NC=2N(CCO)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 AFGOFEFLRMONQO-UHFFFAOYSA-N 0.000 description 1
• TTXCWPOHPCLUKB-UHFFFAOYSA-N 2-amino-1-(2,2-dimethylpropyl)-4-(4-phenoxyphenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(CC(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 TTXCWPOHPCLUKB-UHFFFAOYSA-N 0.000 description 1
• JVDBMLDMYRQVGN-UHFFFAOYSA-N 2-amino-1-cyclopentyl-4-(4-phenoxyphenyl)pyrrole-3-carbonitrile Chemical compound NC1=C(C#N)C(C=2C=CC(OC=3C=CC=CC=3)=CC=2)=CN1C1CCCC1 JVDBMLDMYRQVGN-UHFFFAOYSA-N 0.000 description 1
• OOQSGVDLFZSRGV-UHFFFAOYSA-N 2-amino-1-tert-butyl-4-(4-iodophenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)(C)C)C=C1C1=CC=C(I)C=C1 OOQSGVDLFZSRGV-UHFFFAOYSA-N 0.000 description 1
• JWCOVNSHDJQAIO-UHFFFAOYSA-N 2-amino-1-tert-butyl-4-(4-phenylphenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)(C)C)C=C1C1=CC=C(C=2C=CC=CC=2)C=C1 JWCOVNSHDJQAIO-UHFFFAOYSA-N 0.000 description 1
• KTEZZZQHUOYMMY-UHFFFAOYSA-N 2-amino-1-tert-butyl-4-(4-phenylsulfanylphenyl)pyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)(C)C)C=C1C(C=C1)=CC=C1SC1=CC=CC=C1 KTEZZZQHUOYMMY-UHFFFAOYSA-N 0.000 description 1
• ACWKUXDGUMRIPU-UHFFFAOYSA-N 2-amino-4-(4-phenoxyphenyl)-1-propan-2-ylpyrrole-3-carbonitrile Chemical compound N#CC1=C(N)N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 ACWKUXDGUMRIPU-UHFFFAOYSA-N 0.000 description 1
• XEHFZDUXNKNEFZ-UHFFFAOYSA-N 2-bromo-1-(4-phenylphenyl)ethanethione Chemical compound C1=CC(C(=S)CBr)=CC=C1C1=CC=CC=C1 XEHFZDUXNKNEFZ-UHFFFAOYSA-N 0.000 description 1
• KGHGZRVXCKCJGX-UHFFFAOYSA-N 2-bromo-1-(4-phenylphenyl)ethanone Chemical compound C1=CC(C(=O)CBr)=CC=C1C1=CC=CC=C1 KGHGZRVXCKCJGX-UHFFFAOYSA-N 0.000 description 1
• NPNXBJDANGZWOC-UHFFFAOYSA-N 2-bromo-1-[4-(4-methoxyphenoxy)phenyl]ethanone Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C(=O)CBr)C=C1 NPNXBJDANGZWOC-UHFFFAOYSA-N 0.000 description 1
• LJKQIBWZNUCGSG-UHFFFAOYSA-N 2-chloro-1-(4-iodophenyl)ethanone Chemical compound ClCC(=O)C1=CC=C(I)C=C1 LJKQIBWZNUCGSG-UHFFFAOYSA-N 0.000 description 1
• ICXSHFWYCHJILC-UHFFFAOYSA-N 2-fluoro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1F ICXSHFWYCHJILC-UHFFFAOYSA-N 0.000 description 1
• NUFBIAUZAMHTSP-UHFFFAOYSA-N 3-(n-morpholino)-2-hydroxypropanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CN1CCOCC1 NUFBIAUZAMHTSP-UHFFFAOYSA-N 0.000 description 1
• VBTSHXSAHIROEH-UHFFFAOYSA-N 3-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenoxy]benzamide Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1Cl)=CC=C1OC1=CC=CC(C(N)=O)=C1 VBTSHXSAHIROEH-UHFFFAOYSA-N 0.000 description 1
• NLZQYHOBUFFEFE-UHFFFAOYSA-N 3-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenoxy]phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1Cl)=CC=C1OC1=CC=CC(O)=C1 NLZQYHOBUFFEFE-UHFFFAOYSA-N 0.000 description 1
• KWIISVZUQXBHMT-UHFFFAOYSA-N 3-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC(O)=C1 KWIISVZUQXBHMT-UHFFFAOYSA-N 0.000 description 1
• UJWXPHLWGVGIBB-UHFFFAOYSA-N 3-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentan-1-ol Chemical compound C1=2C(N)=NC=NC=2N(C2CC(O)CC2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 UJWXPHLWGVGIBB-UHFFFAOYSA-N 0.000 description 1
• INEUGWBFDCYOPZ-UHFFFAOYSA-N 3-[4-amino-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]propane-1,2-diol Chemical compound C1=2C(N)=NC=NC=2N(CC(O)CO)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 INEUGWBFDCYOPZ-UHFFFAOYSA-N 0.000 description 1
• IALBWOKSRZOBDJ-UHFFFAOYSA-N 3-[4-chloro-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]propane-1,2-diol Chemical compound C12=C(Cl)N=CN=C2N(CC(O)CO)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 IALBWOKSRZOBDJ-UHFFFAOYSA-N 0.000 description 1
• IWPULBFCJIKASE-UHFFFAOYSA-N 4,4-dimethyl-1-(4-phenoxyphenyl)pentan-1-one;hydrochloride Chemical compound Cl.C1=CC(C(=O)CCC(C)(C)C)=CC=C1OC1=CC=CC=C1 IWPULBFCJIKASE-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
• VSFXNRGZTIKUPB-UHFFFAOYSA-N 4-[4-(4-amino-7-tert-butyl-6,7-dihydropyrrolo[3,2-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound N1=CN=C(N)C2=C1C(C(C)(C)C)CN2C(C=C1)=CC=C1OC1=CC=C(O)C=C1 VSFXNRGZTIKUPB-UHFFFAOYSA-N 0.000 description 1
• YAUXUMSQGNPGQC-UHFFFAOYSA-N 4-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C(O)C=C1 YAUXUMSQGNPGQC-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
• DCRHNWDPEHEXAI-UHFFFAOYSA-N 4-amino-7-tert-butyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-6-ol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C(O)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 DCRHNWDPEHEXAI-UHFFFAOYSA-N 0.000 description 1
• WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
• PTCPUGKKWNMITF-UHFFFAOYSA-N 4-chloro-2-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1F PTCPUGKKWNMITF-UHFFFAOYSA-N 0.000 description 1
• GVFPGTNGIVPDPU-UHFFFAOYSA-N 4-chloro-7-cyclopentyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidine Chemical compound C1=2C(Cl)=NC=NC=2N(C2CCCC2)C=C1C1=CC=CC=C1OC1=CC=CC=C1 GVFPGTNGIVPDPU-UHFFFAOYSA-N 0.000 description 1
• WCPHOIPVDSMEID-UHFFFAOYSA-N 4-cyclopentyl-5-(3-phenoxyphenyl)-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)(C3CCCC3)NC=NC=2NC=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 WCPHOIPVDSMEID-UHFFFAOYSA-N 0.000 description 1
• WLKUSVNHZXUEFO-UHFFFAOYSA-N 4-fluoro-2-methoxy-1-nitrobenzene Chemical compound COC1=CC(F)=CC=C1[N+]([O-])=O WLKUSVNHZXUEFO-UHFFFAOYSA-N 0.000 description 1
• FIXIQTLWTFUPFK-UHFFFAOYSA-N 4-n-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-3-methoxyphenyl]-1-n-methylbenzene-1,4-diamine Chemical compound C1=CC(NC)=CC=C1NC(C=C1OC)=CC=C1C1=CN(C(C)(C)C)C2=NC=NC(N)=C12 FIXIQTLWTFUPFK-UHFFFAOYSA-N 0.000 description 1
• BTYLOGUNBWCOBV-UHFFFAOYSA-N 4-n-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-n-methylbenzene-1,4-diamine Chemical compound C1=CC(NC)=CC=C1NC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 BTYLOGUNBWCOBV-UHFFFAOYSA-N 0.000 description 1
• OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 description 1
• SGMDOGYAVIXLQC-UHFFFAOYSA-N 5-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-(3-chlorophenoxy)phenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1O)=CC=C1OC1=CC=CC(Cl)=C1 SGMDOGYAVIXLQC-UHFFFAOYSA-N 0.000 description 1
• SIGWMCFGIFVKPI-UHFFFAOYSA-N 5-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-phenoxyphenol Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1O)=CC=C1OC1=CC=CC=C1 SIGWMCFGIFVKPI-UHFFFAOYSA-N 0.000 description 1
• IOVZQRIKFGCKNR-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7-(2-phenyl-1,3-dioxan-5-yl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=2C(N)=NC=NC=2N(C2COC(OC2)C=2C=CC=CC=2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 IOVZQRIKFGCKNR-UHFFFAOYSA-N 0.000 description 1
• GTLYPMCHYLJPTD-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 GTLYPMCHYLJPTD-UHFFFAOYSA-N 0.000 description 1
• OBMGVMWHMBYZJC-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-amine;hydrobromide Chemical compound Br.C1=2C(N)=NC=NC=2NC=C1C(C=C1)=CC=C1OC1=CC=CC=C1 OBMGVMWHMBYZJC-UHFFFAOYSA-N 0.000 description 1
• WEVLMNXKWWNNEE-UHFFFAOYSA-N 5-[4-(4-bromophenoxy)phenyl]-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C(Br)C=C1 WEVLMNXKWWNNEE-UHFFFAOYSA-N 0.000 description 1
• RDCVXFCXAMXWDG-UHFFFAOYSA-N 5-[4-(5-chloro-2-nitrophenoxy)phenyl]-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC(Cl)=CC=C1[N+]([O-])=O RDCVXFCXAMXWDG-UHFFFAOYSA-N 0.000 description 1
• VPDWAEBGKFDQTQ-UHFFFAOYSA-N 5-[4-(benzenesulfonyl)phenyl]-7-tert-butylpyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1S(=O)(=O)C1=CC=CC=C1 VPDWAEBGKFDQTQ-UHFFFAOYSA-N 0.000 description 1
• GHYZIXDKAPMFCS-UHFFFAOYSA-N 5-fluoro-2-nitrobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1[N+]([O-])=O GHYZIXDKAPMFCS-UHFFFAOYSA-N 0.000 description 1
• ASZFCDOTGITCJI-UHFFFAOYSA-N 6-oxabicyclo[3.1.0]hex-2-ene Chemical compound C1C=CC2OC12 ASZFCDOTGITCJI-UHFFFAOYSA-N 0.000 description 1
• GJEZBVHHZQAEDB-UHFFFAOYSA-N 6-oxabicyclo[3.1.0]hexane Chemical compound C1CCC2OC21 GJEZBVHHZQAEDB-UHFFFAOYSA-N 0.000 description 1
• NKRZPEDCHVVFBV-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(CC(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NKRZPEDCHVVFBV-UHFFFAOYSA-N 0.000 description 1
• NIYBFYOEORXXTQ-UHFFFAOYSA-N 7-butyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(CCCC)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 NIYBFYOEORXXTQ-UHFFFAOYSA-N 0.000 description 1
• ZQMPTVSCDWLOLC-UHFFFAOYSA-N 7-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 ZQMPTVSCDWLOLC-UHFFFAOYSA-N 0.000 description 1
• LEAHJDMQYBZZGE-UHFFFAOYSA-N 7-tert-butyl-5-(2-chloro-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)Cl)=CC=C1OC1=CC=CC=C1 LEAHJDMQYBZZGE-UHFFFAOYSA-N 0.000 description 1
• BNEWOKNJSGNELA-UHFFFAOYSA-N 7-tert-butyl-5-(2-methoxy-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C(OC)=CC=1OC1=CC=CC=C1 BNEWOKNJSGNELA-UHFFFAOYSA-N 0.000 description 1
• CDYVIWXTUJTTNA-UHFFFAOYSA-N 7-tert-butyl-5-(2-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C1=CC=CC=C1OC1=CC=CC=C1 CDYVIWXTUJTTNA-UHFFFAOYSA-N 0.000 description 1
• QVXCMWDEWYROOR-UHFFFAOYSA-N 7-tert-butyl-5-(3-methoxy-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=CC=C1OC1=CC=CC=C1 QVXCMWDEWYROOR-UHFFFAOYSA-N 0.000 description 1
• QFFYYQQIOGHRFZ-UHFFFAOYSA-N 7-tert-butyl-5-(3-methyl-4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=CC=C1OC1=CC=CC=C1 QFFYYQQIOGHRFZ-UHFFFAOYSA-N 0.000 description 1
• FYSSODXXQJTAER-UHFFFAOYSA-N 7-tert-butyl-5-(3-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 FYSSODXXQJTAER-UHFFFAOYSA-N 0.000 description 1
• UGTRJCYKIPJAHF-UHFFFAOYSA-N 7-tert-butyl-5-[2-chloro-4-(4-chlorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C(=C1)Cl)=CC=C1OC1=CC=C(Cl)C=C1 UGTRJCYKIPJAHF-UHFFFAOYSA-N 0.000 description 1
• GBNOVMOIPFSUDV-UHFFFAOYSA-N 7-tert-butyl-5-[3-chloro-4-(3-chlorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1Cl)=CC=C1OC1=CC=CC(Cl)=C1 GBNOVMOIPFSUDV-UHFFFAOYSA-N 0.000 description 1
• RYBIQZCRZRDGAS-UHFFFAOYSA-N 7-tert-butyl-5-[3-methoxy-4-(3-methylphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=CC=C1OC1=CC=CC(C)=C1 RYBIQZCRZRDGAS-UHFFFAOYSA-N 0.000 description 1
• DSEOXMKMHSTLGC-UHFFFAOYSA-N 7-tert-butyl-5-[3-methyl-4-(3-methylphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(OC=2C(=CC(=CC=2)C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C)=C1 DSEOXMKMHSTLGC-UHFFFAOYSA-N 0.000 description 1
• HMCARUYMUGYRHI-UHFFFAOYSA-N 7-tert-butyl-5-[4-(2-chlorophenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1Cl HMCARUYMUGYRHI-UHFFFAOYSA-N 0.000 description 1
• BTBGEJOUEMJGTG-UHFFFAOYSA-N 7-tert-butyl-5-[4-(2-methoxyphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 BTBGEJOUEMJGTG-UHFFFAOYSA-N 0.000 description 1
• YITGAIYDCLPMAU-UHFFFAOYSA-N 7-tert-butyl-5-[4-(2-methylphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 YITGAIYDCLPMAU-UHFFFAOYSA-N 0.000 description 1
• RULMTNSIRLGMCL-UHFFFAOYSA-N 7-tert-butyl-5-[4-(3-chlorophenoxy)-2-methylphenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C(C)=CC=1OC1=CC=CC(Cl)=C1 RULMTNSIRLGMCL-UHFFFAOYSA-N 0.000 description 1
• GQPJATNKADCJNT-UHFFFAOYSA-N 7-tert-butyl-5-[4-(3-methoxyphenoxy)-3-methylphenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(OC=2C(=CC(=CC=2)C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C)=C1 GQPJATNKADCJNT-UHFFFAOYSA-N 0.000 description 1
• IVHZUGPRQMQRGV-UHFFFAOYSA-N 7-tert-butyl-5-[4-(3-methylphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(OC=2C=CC(=CC=2)C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=C1 IVHZUGPRQMQRGV-UHFFFAOYSA-N 0.000 description 1
• NJMJETJPNGEOHH-UHFFFAOYSA-N 7-tert-butyl-5-[4-(4-methoxyphenoxy)phenyl]-1h-pyrrolo[2,3-d]pyrimidine-4,4-diamine Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C=2C=3C(N)(N)N=CNC=3N(C=2)C(C)(C)C)C=C1 NJMJETJPNGEOHH-UHFFFAOYSA-N 0.000 description 1
• NJSMJBCABAFTHE-UHFFFAOYSA-N 7-tert-butyl-5-[4-(4-methoxyphenoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 NJSMJBCABAFTHE-UHFFFAOYSA-N 0.000 description 1
• FKBDYMVMAZFAFL-UHFFFAOYSA-N 7-tert-butyl-5-[4-[[4-(methylamino)phenyl]methyl]phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=CC(NC)=CC=C1CC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 FKBDYMVMAZFAFL-UHFFFAOYSA-N 0.000 description 1
• QDAFLAVBAXTUQD-UHFFFAOYSA-N 7-tert-butyl-6-chloro-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C(Cl)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 QDAFLAVBAXTUQD-UHFFFAOYSA-N 0.000 description 1
• MGDRFQIBJWGHOQ-UHFFFAOYSA-N 7-tert-butyl-6-methyl-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C(C)=C1C(C=C1)=CC=C1OC1=CC=CC=C1 MGDRFQIBJWGHOQ-UHFFFAOYSA-N 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 208000030090 Acute Disease Diseases 0.000 description 1
• 108010076278 Adenosine kinase Proteins 0.000 description 1
• 102100032534 Adenosine kinase Human genes 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
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 235000003911 Arachis Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• 231100000699 Bacterial toxin Toxicity 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 208000006386 Bone Resorption Diseases 0.000 description 1
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
• 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
• 102000000503 Collagen Type II Human genes 0.000 description 1
• 108010041390 Collagen Type II Proteins 0.000 description 1
• 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
• 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-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
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 208000037147 Hypercalcaemia Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 102000015617 Janus Kinases Human genes 0.000 description 1
• 108010024121 Janus Kinases Proteins 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
• 206010027452 Metastases to bone Diseases 0.000 description 1
• 101100268648 Mus musculus Abl1 gene Proteins 0.000 description 1
• 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
• 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
• 102000047918 Myelin Basic Human genes 0.000 description 1
• 101710107068 Myelin basic protein Proteins 0.000 description 1
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
• GNRVUEAKPMMKEH-UHFFFAOYSA-N NC=1C2=C(N=CN1)N(C=C2C2=CC=C(C=C2)OC2=CC=CC=C2)C(C)(C)C.N2=CN=C(C=C2)N Chemical compound NC=1C2=C(N=CN1)N(C=C2C2=CC=C(C=C2)OC2=CC=CC=C2)C(C)(C)C.N2=CN=C(C=C2)N GNRVUEAKPMMKEH-UHFFFAOYSA-N 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
• 239000012425 OXONE® Substances 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 208000027868 Paget disease Diseases 0.000 description 1
• 201000005702 Pertussis Diseases 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 1
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
• 230000010799 Receptor Interactions Effects 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
• 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 1
• WJUNAUHPHRBPNV-UHFFFAOYSA-N [4-(2-methoxyphenoxy)phenyl]boronic acid Chemical compound COC1=CC=CC=C1OC1=CC=C(B(O)O)C=C1 WJUNAUHPHRBPNV-UHFFFAOYSA-N 0.000 description 1
• 108700025690 abl Genes Proteins 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
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000006242 amine protecting group Chemical group 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000001483 arginine derivatives Chemical class 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 239000000688 bacterial toxin Substances 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 230000024279 bone resorption Effects 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 208000001969 capillary hemangioma Diseases 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 235000015218 chewing gum Nutrition 0.000 description 1
• 239000012320 chlorinating reagent Substances 0.000 description 1
• KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000003501 co-culture Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 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
• 239000006071 cream Substances 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
• XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• FXORZKOZOQWVMQ-UHFFFAOYSA-L dichloropalladium;triphenylphosphane Chemical compound Cl[Pd]Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 FXORZKOZOQWVMQ-UHFFFAOYSA-L 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 210000000624 ear auricle Anatomy 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• OKWOKHLXDJXLNZ-UHFFFAOYSA-N ethyl 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-(3-chlorophenoxy)benzoate Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C(C(=O)OCC)=CC=1OC1=CC=CC(Cl)=C1 OKWOKHLXDJXLNZ-UHFFFAOYSA-N 0.000 description 1
• GHFQEFZKILBJDF-UHFFFAOYSA-N ethyl 2-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-5-phenoxybenzoate Chemical compound C=1C=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C(C(=O)OCC)=CC=1OC1=CC=CC=C1 GHFQEFZKILBJDF-UHFFFAOYSA-N 0.000 description 1
• HQVRYUZYVFRYTD-UHFFFAOYSA-N ethyl 2-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]benzoate Chemical compound CCOC(=O)C1=CC=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 HQVRYUZYVFRYTD-UHFFFAOYSA-N 0.000 description 1
• RKMUWCJOBOWDKN-UHFFFAOYSA-N ethyl 5-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-(3-chlorophenoxy)benzoate Chemical compound CCOC(=O)C1=CC(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=CC=C1OC1=CC=CC(Cl)=C1 RKMUWCJOBOWDKN-UHFFFAOYSA-N 0.000 description 1
• ZKVOLMCBVUYOEQ-UHFFFAOYSA-N ethyl 5-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-phenoxybenzoate Chemical compound CCOC(=O)C1=CC(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)=CC=C1OC1=CC=CC=C1 ZKVOLMCBVUYOEQ-UHFFFAOYSA-N 0.000 description 1
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 210000000416 exudates and transudate Anatomy 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 239000012458 free base Substances 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
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 125000004446 heteroarylalkyl group Chemical group 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
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000000148 hypercalcaemia Effects 0.000 description 1
• 208000030915 hypercalcemia disease Diseases 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000005934 immune activation Effects 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000012336 iodinating agent Substances 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
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 238000005567 liquid scintillation counting Methods 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 208000027202 mammary Paget disease Diseases 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• QLNWXBAGRTUKKI-UHFFFAOYSA-N metacetamol Chemical compound CC(=O)NC1=CC=CC(O)=C1 QLNWXBAGRTUKKI-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• FGNDBHRKHHZLFZ-UHFFFAOYSA-N methyl 4-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-3-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC(C(=O)OC)=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C(C)C)C=2)C=C1 FGNDBHRKHHZLFZ-UHFFFAOYSA-N 0.000 description 1
• CNJJSTPBUHAEFH-UHFFFAOYSA-N methyl 4-fluoro-3-nitrobenzoate Chemical compound COC(=O)C1=CC=C(F)C([N+]([O-])=O)=C1 CNJJSTPBUHAEFH-UHFFFAOYSA-N 0.000 description 1
• 238000001471 micro-filtration Methods 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• YOXWOXDQACBPEQ-UHFFFAOYSA-N n-(2-fluoro-5-nitrophenyl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC([N+]([O-])=O)=CC=C1F YOXWOXDQACBPEQ-UHFFFAOYSA-N 0.000 description 1
• PXJGUIPZTSDKMY-UHFFFAOYSA-N n-(2-fluoro-5-nitrophenyl)acetamide Chemical compound CC(=O)NC1=CC([N+]([O-])=O)=CC=C1F PXJGUIPZTSDKMY-UHFFFAOYSA-N 0.000 description 1
• STOAGEBURGENGQ-UHFFFAOYSA-N n-(4-hydroxyphenyl)-n-methylacetamide Chemical compound CC(=O)N(C)C1=CC=C(O)C=C1 STOAGEBURGENGQ-UHFFFAOYSA-N 0.000 description 1
• OMTRYQCTEWXIAE-UHFFFAOYSA-N n-[2-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-5-nitrophenyl]acetamide Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1NC(C)=O OMTRYQCTEWXIAE-UHFFFAOYSA-N 0.000 description 1
• NWZQESYBXWEOTK-UHFFFAOYSA-N n-[2-[4-(4-amino-7h-pyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]-5-nitrophenyl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC([N+]([O-])=O)=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3NC=2)C=C1 NWZQESYBXWEOTK-UHFFFAOYSA-N 0.000 description 1
• IZZRYPGIYWRQCJ-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-hydroxyphenyl]benzenesulfonamide Chemical compound C1=2C(N)=NC=NC=2N(C2CCCC2)C=C1C(C=C1O)=CC=C1NS(=O)(=O)C1=CC=CC=C1 IZZRYPGIYWRQCJ-UHFFFAOYSA-N 0.000 description 1
• PYGPUAIMCXXAHV-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]benzamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCCC3)C=2)=CC=C1NC(=O)C1=CC=CC=C1 PYGPUAIMCXXAHV-UHFFFAOYSA-N 0.000 description 1
• NNPZHAVLXZLGRT-UHFFFAOYSA-N n-[4-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]benzenesulfonamide Chemical compound COC1=CC(C=2C3=C(N)N=CN=C3N(C3CCCC3)C=2)=CC=C1NS(=O)(=O)C1=CC=CC=C1 NNPZHAVLXZLGRT-UHFFFAOYSA-N 0.000 description 1
• NYROJQHEZOWWIV-UHFFFAOYSA-N n-[4-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]benzamide Chemical compound C12=C(N)N=CN=C2N(C(C)C)C=C1C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 NYROJQHEZOWWIV-UHFFFAOYSA-N 0.000 description 1
• CZHQSLKVMSAZMI-UHFFFAOYSA-N n-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-hydroxyphenyl]naphthalene-2-sulfonamide Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1O)=CC=C1NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 CZHQSLKVMSAZMI-UHFFFAOYSA-N 0.000 description 1
• KIMUSMGBNNQZHJ-UHFFFAOYSA-N n-[4-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)phenoxy]phenyl]-n-methylacetamide Chemical compound C1=CC(N(C(C)=O)C)=CC=C1OC1=CC=C(C=2C3=C(N)N=CN=C3N(C=2)C(C)(C)C)C=C1 KIMUSMGBNNQZHJ-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000027405 negative regulation of phosphorylation Effects 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• VFSBNNSFEZHDPI-UHFFFAOYSA-N oxalic acid;1-(4-phenoxyphenyl)-2-(propan-2-ylamino)ethanone Chemical compound OC(=O)C(O)=O.C1=CC(C(=O)CNC(C)C)=CC=C1OC1=CC=CC=C1 VFSBNNSFEZHDPI-UHFFFAOYSA-N 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 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 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 235000019809 paraffin wax Nutrition 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• YUTHHUZKXISHJH-UHFFFAOYSA-N phenyl n-[4-(4-amino-7-tert-butylpyrrolo[2,3-d]pyrimidin-5-yl)-2-hydroxyphenyl]carbamate Chemical compound C12=C(N)N=CN=C2N(C(C)(C)C)C=C1C(C=C1O)=CC=C1NC(=O)OC1=CC=CC=C1 YUTHHUZKXISHJH-UHFFFAOYSA-N 0.000 description 1
• 210000004214 philadelphia chromosome Anatomy 0.000 description 1
• 229940080469 phosphocellulose Drugs 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011698 potassium fluoride Substances 0.000 description 1
• 235000003270 potassium fluoride Nutrition 0.000 description 1
• OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 230000006337 proteolytic cleavage Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 229920003002 synthetic resin Polymers 0.000 description 1
• 239000000057 synthetic resin Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 150000003899 tartaric acid esters Chemical class 0.000 description 1
• QHBUOTIIVXFTLH-UHFFFAOYSA-N tert-butyl n-(2-methoxy-4-trimethylstannylphenyl)carbamate Chemical compound COC1=CC([Sn](C)(C)C)=CC=C1NC(=O)OC(C)(C)C QHBUOTIIVXFTLH-UHFFFAOYSA-N 0.000 description 1
• CBDHGBOZFSYMEC-UHFFFAOYSA-N tert-butyl n-[4-(4-chloro-7-cyclopentyl-1h-pyrrolo[2,3-d]pyrimidin-4-yl)-2-methoxyphenyl]carbamate Chemical compound C1=C(NC(=O)OC(C)(C)C)C(OC)=CC(C2(Cl)C3=C(N(C=C3)C3CCCC3)NC=N2)=C1 CBDHGBOZFSYMEC-UHFFFAOYSA-N 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
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 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 1
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1