TW201718571A - 經雜芳基取代之胺基吡啶化合物 - Google Patents

Info

Publication number

TW201718571A

TW201718571A TW105119777A TW105119777A TW201718571A TW 201718571 A TW201718571 A TW 201718571A TW 105119777 A TW105119777 A TW 105119777A TW 105119777 A TW105119777 A TW 105119777A TW 201718571 A TW201718571 A TW 201718571A

Authority

TW

Taiwan

Prior art keywords

pyridin

pyridine

pyrazolo

carbonitrile

isopropylamino

Prior art date

2015-06-24

Links

• Espacenet
• Global Dossier
• Discuss

• -1 aminopyridine compounds Chemical class 0.000 title claims abstract description 444
• 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 69
• 150000001875 compounds Chemical class 0.000 claims abstract description 231
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 78
• 150000003839 salts Chemical class 0.000 claims abstract description 74
• 238000011282 treatment Methods 0.000 claims abstract description 32
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
• 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 19
• 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 16
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 15
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 11
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 8
• 125000001425 triazolyl group Chemical group 0.000 claims abstract description 8
• 201000011510 cancer Diseases 0.000 claims abstract description 7
• 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims abstract description 4
• 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 claims abstract description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 144
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 80
• 125000000217 alkyl group Chemical group 0.000 claims description 54
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 52
• 125000002757 morpholinyl group Chemical group 0.000 claims description 46
• 125000001424 substituent group Chemical group 0.000 claims description 44
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 201000010099 disease Diseases 0.000 claims description 32
• 125000003566 oxetanyl group Chemical group 0.000 claims description 32
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 24
• 229910052801 chlorine Inorganic materials 0.000 claims description 21
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 20
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 18
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 18
• 125000003386 piperidinyl group Chemical group 0.000 claims description 17
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
• 229910052731 fluorine Inorganic materials 0.000 claims description 15
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
• 125000004193 piperazinyl group Chemical group 0.000 claims description 15
• 125000002393 azetidinyl group Chemical group 0.000 claims description 14
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
• 239000003937 drug carrier Substances 0.000 claims description 13
• PHJRMOKDBKLWBW-UHFFFAOYSA-N 1-[5-[4-(2-fluoropropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C PHJRMOKDBKLWBW-UHFFFAOYSA-N 0.000 claims description 12
• 201000005569 Gout Diseases 0.000 claims description 11
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
• UZDJXEQNYJMLGI-UHFFFAOYSA-N 1-[5-(1H-imidazol-5-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UZDJXEQNYJMLGI-UHFFFAOYSA-N 0.000 claims description 10
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 10
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• XQGPNSDNLGCYAZ-UHFFFAOYSA-N 1-[5-[1-(1-ethylazetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C XQGPNSDNLGCYAZ-UHFFFAOYSA-N 0.000 claims description 8
• AUWWTOHMKCGNST-UHFFFAOYSA-N 1-[5-[1-(azetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C AUWWTOHMKCGNST-UHFFFAOYSA-N 0.000 claims description 8
• RCVXJIXEMNQHOI-SFHVURJKSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-[[(3S)-oxolan-3-yl]amino]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)N[C@@H]1COCC1)(C)C RCVXJIXEMNQHOI-SFHVURJKSA-N 0.000 claims description 8
• UNJUAEHMTHJIFW-UHFFFAOYSA-N 2-[4-[4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-3-yl]triazol-1-yl]ethanol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1C=CC2=C1N=CN=C2)C=1N=NN(C=1)CCO UNJUAEHMTHJIFW-UHFFFAOYSA-N 0.000 claims description 8
• FVRIGTLYDAWFOA-UHFFFAOYSA-N 3-[5-[4-(2-fluoropropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound FC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)C FVRIGTLYDAWFOA-UHFFFAOYSA-N 0.000 claims description 8
• ZVSYSFPBYMUXLC-UHFFFAOYSA-N 4-[1-[6-(6-aminopyrazolo[3,4-d]pyrimidin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-ol Chemical compound NC1=NC=C2C(=N1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)CCC(C)(O)C)NC(C)C ZVSYSFPBYMUXLC-UHFFFAOYSA-N 0.000 claims description 8
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
• APIIMUUDDPGZDK-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-propylimidazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CCCN1C=NC(=C1)C1=CN=C(C=C1NC(C)C)N1N=CC2=C1N=CC(=C2)C#N APIIMUUDDPGZDK-UHFFFAOYSA-N 0.000 claims description 7
• BFHZKOTWEVQNCP-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N BFHZKOTWEVQNCP-UHFFFAOYSA-N 0.000 claims description 7
• LTXCGBSDENGQFN-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-pyridin-3-ylimidazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=CN(C=1)C=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N LTXCGBSDENGQFN-UHFFFAOYSA-N 0.000 claims description 7
• LACOUNSDJXZNFY-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(1-pyrimidin-2-ylazetidin-3-yl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CN(C1)C1=NC=CC=N1)N1N=CC=2C1=NC=C(C=2)C#N LACOUNSDJXZNFY-UHFFFAOYSA-N 0.000 claims description 7
• MPFUBTOJKFLVCN-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[4-(1-propan-2-ylpiperidin-4-yl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1CCN(CC1)C(C)C)N1N=CC=2C1=NC=C(C=2)C#N MPFUBTOJKFLVCN-UHFFFAOYSA-N 0.000 claims description 7
• SQTPXXVXGVHSHI-UHFFFAOYSA-N 1-[4-[(2-hydroxy-2-methylpropyl)amino]-5-[4-(2-hydroxypropyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CNC1=CC(=NC=C1N1N=NC(=C1)CC(C)O)N1N=CC=2C1=NC=C(C=2)C#N)(C)C SQTPXXVXGVHSHI-UHFFFAOYSA-N 0.000 claims description 7
• ZXJRCPSBIZZWNF-UHFFFAOYSA-N 1-[4-[(3,3-difluorocyclopentyl)amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1(CC(CC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N)F ZXJRCPSBIZZWNF-UHFFFAOYSA-N 0.000 claims description 7
• RWPIMXOOJWJUEZ-UHFFFAOYSA-N 1-[5-(1-ethylpyrazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N1N=CC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C RWPIMXOOJWJUEZ-UHFFFAOYSA-N 0.000 claims description 7
• QDFAFMOTRUAWKR-UHFFFAOYSA-N 1-[5-(1-methyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C)N1N=CC=2C1=NC=C(C=2)C#N QDFAFMOTRUAWKR-UHFFFAOYSA-N 0.000 claims description 7
• GESPJMQHCGMXFX-UHFFFAOYSA-N 1-[5-(4-benzylpyrazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C1=CC=CC=C1)C=1C=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GESPJMQHCGMXFX-UHFFFAOYSA-N 0.000 claims description 7
• UTRSNIMKYCWTMU-UHFFFAOYSA-N 1-[5-[1-(2,3-dihydroxypropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CO UTRSNIMKYCWTMU-UHFFFAOYSA-N 0.000 claims description 7
• GOICDGNZHFRGGP-UHFFFAOYSA-N 1-[5-[1-(2-methylpropyl)imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C(C)C)N1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GOICDGNZHFRGGP-UHFFFAOYSA-N 0.000 claims description 7
• FFZRTARGPDRNMH-UHFFFAOYSA-N 1-[5-[1-(3-aminopropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C FFZRTARGPDRNMH-UHFFFAOYSA-N 0.000 claims description 7
• VRHDEKLMJZOATP-NRFANRHFSA-N 1-[5-[1-[(2S)-2-amino-3-phenylpropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N[C@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CC1=CC=CC=C1 VRHDEKLMJZOATP-NRFANRHFSA-N 0.000 claims description 7
• QCYBEIUZSYEGNW-FXAWDEMLSA-N 1-[5-[1-[(3S,4R)-3-fluoropiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC(C)NC1=CC(=NC=C1C1=CN(N=N1)[C@@H]1CCNC[C@@H]1F)N1N=CC2=C1N=CC(=C2)C#N QCYBEIUZSYEGNW-FXAWDEMLSA-N 0.000 claims description 7
• SFUBJXVEVCGZIJ-UHFFFAOYSA-N 1-[5-[4-(2-hydroxyethyl)pyrazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCC=1C=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C SFUBJXVEVCGZIJ-UHFFFAOYSA-N 0.000 claims description 7
• JXQNQOVNQHVKBX-UHFFFAOYSA-N 1-[5-[4-(benzenesulfonylmethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CS(=O)(=O)C1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N JXQNQOVNQHVKBX-UHFFFAOYSA-N 0.000 claims description 7
• CBELNQDWSSWNEI-UHFFFAOYSA-N 1-[5-[4-(fluoromethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C CBELNQDWSSWNEI-UHFFFAOYSA-N 0.000 claims description 7
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 229960004979 fampridine Drugs 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• AWYBFCCJEGJOQC-HXUWFJFHSA-N tert-butyl (2R)-2-[[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]methyl]pyrrolidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)C[C@@H]1N(CCC1)C(=O)OC(C)(C)C)NC(C)C AWYBFCCJEGJOQC-HXUWFJFHSA-N 0.000 claims description 7
• ZMNYBXBGSRSANG-XZOQPEGZSA-N tert-butyl (3R,4S)-4-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-hydroxypiperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)[C@@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)O)NC(C)C ZMNYBXBGSRSANG-XZOQPEGZSA-N 0.000 claims description 7
• WZIREXKRVWFWDY-UHFFFAOYSA-N tert-butyl 3-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]azetidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CC(C1)N1N=NC(=C1)C=1C=NC(=CC=1NC(C)C)N1N=CC=2C1=NC=C(C=2)C#N WZIREXKRVWFWDY-UHFFFAOYSA-N 0.000 claims description 7
• DNZHYKKVLHEBDU-UHFFFAOYSA-N tert-butyl 4-[1-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]piperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)C1CCN(CC1)C(=O)OC(C)(C)C)NC(C)C DNZHYKKVLHEBDU-UHFFFAOYSA-N 0.000 claims description 7
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 7
• ZOEPGDLOKCFSAJ-WOJBJXKFSA-N 1-[4-(cyclopropylamino)-5-[1-[(3R,4R)-4-hydroxypiperidin-3-yl]triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)[C@@H]1CNCC[C@H]1O)N1N=CC=2C1=NC=C(C=2)C#N ZOEPGDLOKCFSAJ-WOJBJXKFSA-N 0.000 claims description 6
• UVTKYUPIONLULP-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-prop-2-enyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC(C)NC1=CC(=NC=C1N1C=C(CC=C)N=N1)N1N=CC2=C1N=CC(=C2)C#N UVTKYUPIONLULP-UHFFFAOYSA-N 0.000 claims description 6
• CNAUUJIWAQALDJ-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(1-propan-2-ylazetidin-3-yl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CN(C1)C(C)C)N1N=CC=2C1=NC=C(C=2)C#N CNAUUJIWAQALDJ-UHFFFAOYSA-N 0.000 claims description 6
• SGTGXXLTWWAIDL-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)CC(F)(F)F)N1N=CC=2C1=NC=C(C=2)C#N SGTGXXLTWWAIDL-UHFFFAOYSA-N 0.000 claims description 6
• BDFMURFKCOGSJE-UHFFFAOYSA-N 1-[5-[1-(2-aminoethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C BDFMURFKCOGSJE-UHFFFAOYSA-N 0.000 claims description 6
• SKILFDZRXZHTES-UHFFFAOYSA-N 1-[5-[1-(2-hydroxy-2-methylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C SKILFDZRXZHTES-UHFFFAOYSA-N 0.000 claims description 6
• IWFABHLRWIUEBE-UHFFFAOYSA-N 1-[5-[1-(oxetan-3-ylmethyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)CC1COC1)N1N=CC=2C1=NC=C(C=2)C#N IWFABHLRWIUEBE-UHFFFAOYSA-N 0.000 claims description 6
• VRHDEKLMJZOATP-OAQYLSRUSA-N 1-[5-[1-[(2R)-2-amino-3-phenylpropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N[C@@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CC1=CC=CC=C1 VRHDEKLMJZOATP-OAQYLSRUSA-N 0.000 claims description 6
• CWDBPSSQTVFNHA-VQTJNVASSA-N 1-[5-[1-[(3R,4S)-3-hydroxypiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H]1CNCC[C@@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C CWDBPSSQTVFNHA-VQTJNVASSA-N 0.000 claims description 6
• KUBKRYARXKXMBP-UHFFFAOYSA-N 1-[5-[4-(2-fluoro-3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C(C)(C)O KUBKRYARXKXMBP-UHFFFAOYSA-N 0.000 claims description 6
• INIUJJWAZORIKR-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-5-(1-methyltriazol-4-yl)-N-propan-2-ylpyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C INIUJJWAZORIKR-UHFFFAOYSA-N 0.000 claims description 6
• NNTWBCGIWBDHBF-ZDUSSCGKSA-N 3-[4-[[(2S)-1-hydroxypropan-2-yl]amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC[C@H](C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1C=NC=2C1=NC=C(C=2)C#N NNTWBCGIWBDHBF-ZDUSSCGKSA-N 0.000 claims description 6
• IVTKZLIVZAQJIK-RTBURBONSA-N 3-[5-[1-[(3R,4S)-4-hydroxyoxolan-3-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound O[C@H]1[C@@H](COC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C IVTKZLIVZAQJIK-RTBURBONSA-N 0.000 claims description 6
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
• 208000011231 Crohn disease Diseases 0.000 claims description 6
• 206010016207 Familial Mediterranean fever Diseases 0.000 claims description 6
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 6
• 201000004681 Psoriasis Diseases 0.000 claims description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 6
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
• 208000024908 graft versus host disease Diseases 0.000 claims description 6
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 5
• FISDAMCSXFSJMO-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N FISDAMCSXFSJMO-UHFFFAOYSA-N 0.000 claims description 5
• ZKNNTZMYAGDKCS-UHFFFAOYSA-N 1-[5-[1-(2-hydroxyethyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCN1N=CC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C ZKNNTZMYAGDKCS-UHFFFAOYSA-N 0.000 claims description 5
• GYAQOSRWXISIGQ-UHFFFAOYSA-N 1-[5-[1-(cyclobutylmethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CCC1)CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GYAQOSRWXISIGQ-UHFFFAOYSA-N 0.000 claims description 5
• PEEMGCUQEXWCLE-UHFFFAOYSA-N 1-[5-[4-(hydroxymethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C PEEMGCUQEXWCLE-UHFFFAOYSA-N 0.000 claims description 5
• UOZAXLWMFIKWHM-UHFFFAOYSA-N 3-[5-[1-(1-methylazetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CN(C1)C)N1C=NC=2C1=NC=C(C=2)C#N UOZAXLWMFIKWHM-UHFFFAOYSA-N 0.000 claims description 5
• HLJTUCUISGMZIO-UHFFFAOYSA-N 5-[1-(2-morpholin-4-ylethyl)triazol-4-yl]-N-propan-2-yl-2-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-4-amine Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCN1CCOCC1)N1C=CC2=C1N=CN=C2 HLJTUCUISGMZIO-UHFFFAOYSA-N 0.000 claims description 5
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 5
• 208000006673 asthma Diseases 0.000 claims description 5
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 5
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
• WDKWTXHBEQGLDD-RTBURBONSA-N (3R,4R)-4-[4-[4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-3-yl]triazol-1-yl]piperidin-3-ol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1C=CC2=C1N=CN=C2)C=1N=NN(C=1)[C@H]1[C@@H](CNCC1)O WDKWTXHBEQGLDD-RTBURBONSA-N 0.000 claims description 4
• WDKWTXHBEQGLDD-RBUKOAKNSA-N (3R,4S)-4-[4-[4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-3-yl]triazol-1-yl]piperidin-3-ol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1C=CC2=C1N=CN=C2)C=1N=NN(C=1)[C@@H]1[C@@H](CNCC1)O WDKWTXHBEQGLDD-RBUKOAKNSA-N 0.000 claims description 4
• WDKWTXHBEQGLDD-MOPGFXCFSA-N (3S,4R)-4-[4-[4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-3-yl]triazol-1-yl]piperidin-3-ol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1C=CC2=C1N=CN=C2)C=1N=NN(C=1)[C@H]1[C@H](CNCC1)O WDKWTXHBEQGLDD-MOPGFXCFSA-N 0.000 claims description 4
• BTFALHXDRSQHBG-UHFFFAOYSA-N 1-[4-(1,3-difluoropropan-2-ylamino)-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FCC(CF)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N BTFALHXDRSQHBG-UHFFFAOYSA-N 0.000 claims description 4
• HAYSITQQLQFXBO-UHFFFAOYSA-N 1-[4-(3-fluoropropylamino)-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FCCCNC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N HAYSITQQLQFXBO-UHFFFAOYSA-N 0.000 claims description 4
• SLJGCBAKNPTWGK-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N SLJGCBAKNPTWGK-UHFFFAOYSA-N 0.000 claims description 4
• AICFJWOBYXGBOR-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-5-[1-(2-hydroxyethyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)CCO)N1N=CC=2C1=NC=C(C=2)C#N AICFJWOBYXGBOR-UHFFFAOYSA-N 0.000 claims description 4
• RWZHPKWFPPNOAS-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-5-[1-(2-morpholin-4-ylethyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)CCN1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N RWZHPKWFPPNOAS-UHFFFAOYSA-N 0.000 claims description 4
• WFNOKOSBVRRUMF-UHFFFAOYSA-N 1-[4-(ethylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N WFNOKOSBVRRUMF-UHFFFAOYSA-N 0.000 claims description 4
• BRLVYDZLHTZRNR-LBPRGKRZSA-N 1-[4-(ethylamino)-5-[1-[(2S)-2-hydroxypropyl]triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)NC1=CC(=NC=C1C=1N=NN(C=1)C[C@H](C)O)N1N=CC=2C1=NC=C(C=2)C#N BRLVYDZLHTZRNR-LBPRGKRZSA-N 0.000 claims description 4
• NFXCQYWCKQXKNH-UHFFFAOYSA-N 1-[4-(ethylamino)-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N NFXCQYWCKQXKNH-UHFFFAOYSA-N 0.000 claims description 4
• ZESIGJFOISDZIJ-UHFFFAOYSA-N 1-[4-(oxetan-3-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O1CC(C1)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N ZESIGJFOISDZIJ-UHFFFAOYSA-N 0.000 claims description 4
• MXWVCUXJWOWCTN-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-propan-2-ylimidazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)N1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C MXWVCUXJWOWCTN-UHFFFAOYSA-N 0.000 claims description 4
• VQBFAZMYAWDDPS-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-propylpyrazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N VQBFAZMYAWDDPS-UHFFFAOYSA-N 0.000 claims description 4
• MARCUDOQBUCAPS-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-pyridin-3-yltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N MARCUDOQBUCAPS-UHFFFAOYSA-N 0.000 claims description 4
• JLHUXFZZGWKDJM-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(3-pyridin-3-ylpyrazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=C(C=C1)C=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N JLHUXFZZGWKDJM-UHFFFAOYSA-N 0.000 claims description 4
• ITEMVTJVEKQTTA-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-propan-2-ylpyrazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)C=1C=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C ITEMVTJVEKQTTA-UHFFFAOYSA-N 0.000 claims description 4
• CRJPJJGTZVBXSH-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-pyridin-2-ylpyrazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=CC(=C1)C1=NC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N CRJPJJGTZVBXSH-UHFFFAOYSA-N 0.000 claims description 4
• LJNRWIYEFFPOMY-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-pyridin-2-yltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1=NC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N LJNRWIYEFFPOMY-UHFFFAOYSA-N 0.000 claims description 4
• BIVUPILKVLGWCD-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-pyridin-4-yltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1=CC=NC=C1)N1N=CC=2C1=NC=C(C=2)C#N BIVUPILKVLGWCD-UHFFFAOYSA-N 0.000 claims description 4
• YSDWHWCHMACVGC-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(2-pyridin-2-ylethyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC1=NC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N YSDWHWCHMACVGC-UHFFFAOYSA-N 0.000 claims description 4
• ZICCFWLRNRLUAR-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(2-pyridin-3-ylethyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N ZICCFWLRNRLUAR-UHFFFAOYSA-N 0.000 claims description 4
• YYFVUEHTWZKBEX-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(2-pyridin-4-ylethyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC1=CC=NC=C1)N1N=CC=2C1=NC=C(C=2)C#N YYFVUEHTWZKBEX-UHFFFAOYSA-N 0.000 claims description 4
• VNMBWKIBKVDUQH-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(3,3,3-trifluoro-2-hydroxypropyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CC(C(F)(F)F)O)N1N=CC=2C1=NC=C(C=2)C#N VNMBWKIBKVDUQH-UHFFFAOYSA-N 0.000 claims description 4
• XWBDFMDMJONMGG-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(3,3,3-trifluoropropyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC(F)(F)F)N1N=CC=2C1=NC=C(C=2)C#N XWBDFMDMJONMGG-UHFFFAOYSA-N 0.000 claims description 4
• YRAPQPQUWJQZMF-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(3-pyrrolidin-1-ylpropyl)triazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCCN1CCCC1)N1N=CC=2C1=NC=C(C=2)C#N YRAPQPQUWJQZMF-UHFFFAOYSA-N 0.000 claims description 4
• HNMRNLZZMIYBDI-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(pyridin-2-ylmethyl)imidazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=CN(C=1)CC1=NC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N HNMRNLZZMIYBDI-UHFFFAOYSA-N 0.000 claims description 4
• YDYCDZAGEVISQN-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[1-(pyridin-3-ylmethyl)imidazol-4-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=CN(C=1)CC=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N YDYCDZAGEVISQN-UHFFFAOYSA-N 0.000 claims description 4
• KMIGKYSMQFLLAI-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-[3-(trifluoromethyl)pyrazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=C(C=C1)C(F)(F)F)N1N=CC=2C1=NC=C(C=2)C#N KMIGKYSMQFLLAI-UHFFFAOYSA-N 0.000 claims description 4
• HTLVCKVFRXJLLQ-UHFFFAOYSA-N 1-[4-[(1-ethylpyrazol-4-yl)amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N1N=CC(=C1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N HTLVCKVFRXJLLQ-UHFFFAOYSA-N 0.000 claims description 4
• UKCXYUPFRNFGBV-UHFFFAOYSA-N 1-[4-[(2-hydroxy-2-methylpropyl)amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CNC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N)(C)C UKCXYUPFRNFGBV-UHFFFAOYSA-N 0.000 claims description 4
• PUOOZNAGTWJNDI-UHFFFAOYSA-N 1-[4-[(3,3-difluorocyclobutyl)amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1(CC(C1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N)F PUOOZNAGTWJNDI-UHFFFAOYSA-N 0.000 claims description 4
• ILTURIUIZYWDGR-UHFFFAOYSA-N 1-[4-[(3-fluorocyclopentyl)amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1CC(CC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N ILTURIUIZYWDGR-UHFFFAOYSA-N 0.000 claims description 4
• LNKUFPHUASVECL-UHFFFAOYSA-N 1-[4-[(4-fluorooxolan-3-yl)amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1C(COC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N LNKUFPHUASVECL-UHFFFAOYSA-N 0.000 claims description 4
• ILTURIUIZYWDGR-MSOLQXFVSA-N 1-[4-[[(1S,3R)-3-fluorocyclopentyl]amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound F[C@H]1C[C@H](CC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N ILTURIUIZYWDGR-MSOLQXFVSA-N 0.000 claims description 4
• ILTURIUIZYWDGR-ROUUACIJSA-N 1-[4-[[(1S,3S)-3-fluorocyclopentyl]amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound F[C@@H]1C[C@H](CC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N ILTURIUIZYWDGR-ROUUACIJSA-N 0.000 claims description 4
• AFKCXNDYRDTDFL-CYBMUJFWSA-N 1-[4-[[(2R)-1-hydroxypropan-2-yl]amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@@H](C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N AFKCXNDYRDTDFL-CYBMUJFWSA-N 0.000 claims description 4
• WCFWKNTYYISRNT-ZDUSSCGKSA-N 1-[4-[[(2S)-1-hydroxypropan-2-yl]amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@H](C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N WCFWKNTYYISRNT-ZDUSSCGKSA-N 0.000 claims description 4
• AFKCXNDYRDTDFL-ZDUSSCGKSA-N 1-[4-[[(2S)-1-hydroxypropan-2-yl]amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@H](C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N AFKCXNDYRDTDFL-ZDUSSCGKSA-N 0.000 claims description 4
• NGZZECNYMIIQDH-UHFFFAOYSA-N 1-[4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=C(C=2)C#N)F NGZZECNYMIIQDH-UHFFFAOYSA-N 0.000 claims description 4
• QYWVVTPNRHZJIA-UHFFFAOYSA-N 1-[5-(1-benzylimidazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C1=CC=CC=C1)N1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C QYWVVTPNRHZJIA-UHFFFAOYSA-N 0.000 claims description 4
• BLOBHGLAQJGYLE-UHFFFAOYSA-N 1-[5-(1-benzyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C1=CC=CC=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C BLOBHGLAQJGYLE-UHFFFAOYSA-N 0.000 claims description 4
• JLOLQDDVRDMFPZ-UHFFFAOYSA-N 1-[5-(1-cyclohexyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CCCCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C JLOLQDDVRDMFPZ-UHFFFAOYSA-N 0.000 claims description 4
• GZLLTCBFIZUKFY-UHFFFAOYSA-N 1-[5-(1-cyclopropylpyrazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)N1N=CC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GZLLTCBFIZUKFY-UHFFFAOYSA-N 0.000 claims description 4
• XALSLLZSBJCAMW-UHFFFAOYSA-N 1-[5-(1-ethylimidazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C XALSLLZSBJCAMW-UHFFFAOYSA-N 0.000 claims description 4
• RYDCIKCZAKRXMW-UHFFFAOYSA-N 1-[5-(1-ethyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C RYDCIKCZAKRXMW-UHFFFAOYSA-N 0.000 claims description 4
• OUHVERMVYFZTOV-UHFFFAOYSA-N 1-[5-(1-phenyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N OUHVERMVYFZTOV-UHFFFAOYSA-N 0.000 claims description 4
• UIUSHGXVUVOIBW-UHFFFAOYSA-N 1-[5-(1-piperidin-4-yltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CCNCC1)N1N=CC=2C1=NC=C(C=2)C#N UIUSHGXVUVOIBW-UHFFFAOYSA-N 0.000 claims description 4
• GZYPBPRROAQLHO-UHFFFAOYSA-N 1-[5-(1-tert-butyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)(C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GZYPBPRROAQLHO-UHFFFAOYSA-N 0.000 claims description 4
• BJCITYDEBYHMPO-UHFFFAOYSA-N 1-[5-(3-cyanopyrazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)C1=NN(C=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C BJCITYDEBYHMPO-UHFFFAOYSA-N 0.000 claims description 4
• SLQVMMADSWPCID-UHFFFAOYSA-N 1-[5-(3-methylpyrazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=C(C=C1)C)N1N=CC=2C1=NC=C(C=2)C#N SLQVMMADSWPCID-UHFFFAOYSA-N 0.000 claims description 4
• MXONRMNAAMNYRY-UHFFFAOYSA-N 1-[5-(3-morpholin-3-yl-1,2-oxazol-5-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C1=CC(=NO1)C1NCCOC1)N1N=CC=2C1=NC=C(C=2)C#N MXONRMNAAMNYRY-UHFFFAOYSA-N 0.000 claims description 4
• HLUBXJPMMWMTCU-UHFFFAOYSA-N 1-[5-(4-butyltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(CCC)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C HLUBXJPMMWMTCU-UHFFFAOYSA-N 0.000 claims description 4
• OAOGELZINFEHHX-UHFFFAOYSA-N 1-[5-(4-cyclopentyltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CCCC1)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OAOGELZINFEHHX-UHFFFAOYSA-N 0.000 claims description 4
• WMOWXLREOYRBKV-UHFFFAOYSA-N 1-[5-(4-cyclopropyltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C WMOWXLREOYRBKV-UHFFFAOYSA-N 0.000 claims description 4
• OQHUKXPHNVUYKZ-UHFFFAOYSA-N 1-[5-(4-ethyltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OQHUKXPHNVUYKZ-UHFFFAOYSA-N 0.000 claims description 4
• JEQHZOBLAJOJAH-UHFFFAOYSA-N 1-[5-(4-phenyltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N JEQHZOBLAJOJAH-UHFFFAOYSA-N 0.000 claims description 4
• VDYKDCYJTILICN-UHFFFAOYSA-N 1-[5-[1-(1-benzhydrylazetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C VDYKDCYJTILICN-UHFFFAOYSA-N 0.000 claims description 4
• GGKYTKSFKPJMMA-UHFFFAOYSA-N 1-[5-[1-(1-cyanoazetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GGKYTKSFKPJMMA-UHFFFAOYSA-N 0.000 claims description 4
• QUUWSBJXAAYZSG-UHFFFAOYSA-N 1-[5-[1-(1-methylsulfonylpiperidin-4-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CCN(CC1)S(=O)(=O)C)N1N=CC=2C1=NC=C(C=2)C#N QUUWSBJXAAYZSG-UHFFFAOYSA-N 0.000 claims description 4
• VGEDKLMAYHYXNY-UHFFFAOYSA-N 1-[5-[1-(1-phenylethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C(C)C1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N VGEDKLMAYHYXNY-UHFFFAOYSA-N 0.000 claims description 4
• MGSCQJIBMQMADM-UHFFFAOYSA-N 1-[5-[1-(1H-benzimidazol-2-ylmethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N1C(=NC2=C1C=CC=C2)CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C MGSCQJIBMQMADM-UHFFFAOYSA-N 0.000 claims description 4
• VCMCILLYSCPAOE-UHFFFAOYSA-N 1-[5-[1-(2,2-difluoroethyl)imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)F VCMCILLYSCPAOE-UHFFFAOYSA-N 0.000 claims description 4
• IFHPEMVRTNNUEF-UHFFFAOYSA-N 1-[5-[1-(2-cyanophenyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)C1=C(C=CC=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C IFHPEMVRTNNUEF-UHFFFAOYSA-N 0.000 claims description 4
• RFFNOUQJOOPUDT-UHFFFAOYSA-N 1-[5-[1-(2-cyanopyridin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)C1=NC=CC=C1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C RFFNOUQJOOPUDT-UHFFFAOYSA-N 0.000 claims description 4
• OOPTWDRDEQBPRY-UHFFFAOYSA-N 1-[5-[1-(2-ethoxyethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)OCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OOPTWDRDEQBPRY-UHFFFAOYSA-N 0.000 claims description 4
• YLYBNASRFJCAHV-UHFFFAOYSA-N 1-[5-[1-(2-fluorophenyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1=C(C=CC=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C YLYBNASRFJCAHV-UHFFFAOYSA-N 0.000 claims description 4
• AUUDQVSCLJRITL-UHFFFAOYSA-N 1-[5-[1-(2-hydroxy-3-methylbutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C(C)C AUUDQVSCLJRITL-UHFFFAOYSA-N 0.000 claims description 4
• MRLZURSOZPGJCR-UHFFFAOYSA-N 1-[5-[1-(2-methoxyethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCOC)N1N=CC=2C1=NC=C(C=2)C#N MRLZURSOZPGJCR-UHFFFAOYSA-N 0.000 claims description 4
• OBXIRKJVYBHDAX-UHFFFAOYSA-N 1-[5-[1-(2-methylpropyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C(C)C)N1N=CC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OBXIRKJVYBHDAX-UHFFFAOYSA-N 0.000 claims description 4
• ZSTYMKGMLZQXMA-UHFFFAOYSA-N 1-[5-[1-(2-methylsulfonylethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCS(=O)(=O)C)N1N=CC=2C1=NC=C(C=2)C#N ZSTYMKGMLZQXMA-UHFFFAOYSA-N 0.000 claims description 4
• XVTYYVJPONNJIA-UHFFFAOYSA-N 1-[5-[1-(2-morpholin-4-ylethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCN1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N XVTYYVJPONNJIA-UHFFFAOYSA-N 0.000 claims description 4
• OXWXKXZGTOUWDI-UHFFFAOYSA-N 1-[5-[1-(3-cyano-4-fluorophenyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)C=1C=C(C=CC=1F)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OXWXKXZGTOUWDI-UHFFFAOYSA-N 0.000 claims description 4
• WEZGMFJYJIOIJR-UHFFFAOYSA-N 1-[5-[1-(3-fluoropropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C WEZGMFJYJIOIJR-UHFFFAOYSA-N 0.000 claims description 4
• UOSSKRBYOFVUDO-UHFFFAOYSA-N 1-[5-[1-(3-hydroxy-3-methylbutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C UOSSKRBYOFVUDO-UHFFFAOYSA-N 0.000 claims description 4
• IPXFYLMXKDCHJJ-UHFFFAOYSA-N 1-[5-[1-(3-hydroxyphenyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC=1C=C(C=CC=1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C IPXFYLMXKDCHJJ-UHFFFAOYSA-N 0.000 claims description 4
• GWMLNXLPNXBBRB-UHFFFAOYSA-N 1-[5-[1-(3-hydroxypropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GWMLNXLPNXBBRB-UHFFFAOYSA-N 0.000 claims description 4
• IITKWYKANWOTNB-UHFFFAOYSA-N 1-[5-[1-(3-phenylpropyl)imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=CN(C=1)CCCC1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N IITKWYKANWOTNB-UHFFFAOYSA-N 0.000 claims description 4
• XOBRVSUSERJWSJ-UHFFFAOYSA-N 1-[5-[1-(3-phenylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCCC1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N XOBRVSUSERJWSJ-UHFFFAOYSA-N 0.000 claims description 4
• LGJLIHJFZIPZOY-UHFFFAOYSA-N 1-[5-[1-(4-fluorobutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FCCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C LGJLIHJFZIPZOY-UHFFFAOYSA-N 0.000 claims description 4
• GGRAWYSSBLFZLF-UHFFFAOYSA-N 1-[5-[1-(4-fluorophenyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1=CC=C(C=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GGRAWYSSBLFZLF-UHFFFAOYSA-N 0.000 claims description 4
• JAQGTROFTIWFBG-UHFFFAOYSA-N 1-[5-[1-(4-hydroxybutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C JAQGTROFTIWFBG-UHFFFAOYSA-N 0.000 claims description 4
• RIEFICBDDKFVMP-UHFFFAOYSA-N 1-[5-[1-(5-aminopentyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCCCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C RIEFICBDDKFVMP-UHFFFAOYSA-N 0.000 claims description 4
• MWVLHMHOLKMYMH-UHFFFAOYSA-N 1-[5-[1-(5-hydroxypentyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C MWVLHMHOLKMYMH-UHFFFAOYSA-N 0.000 claims description 4
• UBMZMWPXQBEZCW-UHFFFAOYSA-N 1-[5-[1-(cyanomethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UBMZMWPXQBEZCW-UHFFFAOYSA-N 0.000 claims description 4
• UAKXTRKWNJDLPB-UHFFFAOYSA-N 1-[5-[1-(cyclobutylmethyl)imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CCC1)CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UAKXTRKWNJDLPB-UHFFFAOYSA-N 0.000 claims description 4
• DEMIRDKJAZCIKQ-UHFFFAOYSA-N 1-[5-[1-(cyclopropylmethyl)imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C DEMIRDKJAZCIKQ-UHFFFAOYSA-N 0.000 claims description 4
• YKFRQVKESUKZHO-UHFFFAOYSA-N 1-[5-[1-(cyclopropylmethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C YKFRQVKESUKZHO-UHFFFAOYSA-N 0.000 claims description 4
• KBVKVOIFJJZVEI-UHFFFAOYSA-N 1-[5-[1-(difluoromethyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(N1N=CC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)F KBVKVOIFJJZVEI-UHFFFAOYSA-N 0.000 claims description 4
• SFPYMDUQDKMWLQ-UHFFFAOYSA-N 1-[5-[1-(oxetan-2-ylmethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CC1OCC1)N1N=CC=2C1=NC=C(C=2)C#N SFPYMDUQDKMWLQ-UHFFFAOYSA-N 0.000 claims description 4
• YAUIUEXABJLVBD-UHFFFAOYSA-N 1-[5-[1-(oxetan-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1COC1)N1N=CC=2C1=NC=C(C=2)C#N YAUIUEXABJLVBD-UHFFFAOYSA-N 0.000 claims description 4
• OCVYNVMYNRHDQO-QHCPKHFHSA-N 1-[5-[1-[(1R)-2-hydroxy-1-phenylethyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@@H](C1=CC=CC=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OCVYNVMYNRHDQO-QHCPKHFHSA-N 0.000 claims description 4
• QFYHXVPDUXUCRE-ZJSXRUAMSA-N 1-[5-[1-[(1R,2R)-2-hydroxy-2-methylcyclohexyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@]1([C@@H](CCCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C QFYHXVPDUXUCRE-ZJSXRUAMSA-N 0.000 claims description 4
• SGTKJAPSTWEBRU-NHCUHLMSSA-N 1-[5-[1-[(1R,2R)-2-hydroxycyclohexyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]1[C@@H](CCCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C SGTKJAPSTWEBRU-NHCUHLMSSA-N 0.000 claims description 4
• OCVYNVMYNRHDQO-HSZRJFAPSA-N 1-[5-[1-[(1S)-2-hydroxy-1-phenylethyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@H](C1=CC=CC=C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C OCVYNVMYNRHDQO-HSZRJFAPSA-N 0.000 claims description 4
• SGTKJAPSTWEBRU-LEWJYISDSA-N 1-[5-[1-[(1S,2R)-2-hydroxycyclohexyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]1[C@H](CCCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C SGTKJAPSTWEBRU-LEWJYISDSA-N 0.000 claims description 4
• BBJXHULXANBCKM-UHFFFAOYSA-N 1-[5-[1-[(2-methyl-1,3-benzothiazol-5-yl)methyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CC=1C=CC2=C(N=C(S2)C)C=1)N1N=CC=2C1=NC=C(C=2)C#N BBJXHULXANBCKM-UHFFFAOYSA-N 0.000 claims description 4
• UHXFMQJYIGYPGA-QHCPKHFHSA-N 1-[5-[1-[(2R)-2-hydroxy-2-phenylethyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C1=CC=CC=C1 UHXFMQJYIGYPGA-QHCPKHFHSA-N 0.000 claims description 4
• KABVKRYOIRXXRB-CYBMUJFWSA-N 1-[5-[1-[(2R)-2-hydroxypropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C KABVKRYOIRXXRB-CYBMUJFWSA-N 0.000 claims description 4
• UHXFMQJYIGYPGA-HSZRJFAPSA-N 1-[5-[1-[(2S)-2-hydroxy-2-phenylethyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C1=CC=CC=C1 UHXFMQJYIGYPGA-HSZRJFAPSA-N 0.000 claims description 4
• AVIPMWLLNUBRHH-INIZCTEOSA-N 1-[5-[1-[(2S)-2-hydroxybutyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CC AVIPMWLLNUBRHH-INIZCTEOSA-N 0.000 claims description 4
• KABVKRYOIRXXRB-ZDUSSCGKSA-N 1-[5-[1-[(2S)-2-hydroxypropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C KABVKRYOIRXXRB-ZDUSSCGKSA-N 0.000 claims description 4
• ZIOXBSVBHXGESR-HNNXBMFYSA-N 1-[5-[1-[(2S)-3-hydroxy-2-methylpropyl]imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC[C@H](CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C ZIOXBSVBHXGESR-HNNXBMFYSA-N 0.000 claims description 4
• GBYXJRJXGWQDCI-RTWAWAEBSA-N 1-[5-[1-[(3S,4R)-3-hydroxy-1-methylsulfonylpiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]1CN(CC[C@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)S(=O)(=O)C GBYXJRJXGWQDCI-RTWAWAEBSA-N 0.000 claims description 4
• CWDBPSSQTVFNHA-UXHICEINSA-N 1-[5-[1-[(3S,4R)-3-hydroxypiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]1CNCC[C@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C CWDBPSSQTVFNHA-UXHICEINSA-N 0.000 claims description 4
• RYJIDYNPFBMSRT-MOPGFXCFSA-N 1-[5-[1-[(3S,4R)-3-hydroxypiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carboxamide Chemical compound O[C@H]1CNCC[C@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C(=O)N)NC(C)C RYJIDYNPFBMSRT-MOPGFXCFSA-N 0.000 claims description 4
• UPVCRCKCIOWONA-UHFFFAOYSA-N 1-[5-[1-[(4-methoxyphenyl)methyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CC1=CC=C(C=C1)OC)N1N=CC=2C1=NC=C(C=2)C#N UPVCRCKCIOWONA-UHFFFAOYSA-N 0.000 claims description 4
• NXTYKRONDSTYMX-UHFFFAOYSA-N 1-[5-[1-[1-(cyclopropanecarbonyl)azetidin-3-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)C(=O)N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C NXTYKRONDSTYMX-UHFFFAOYSA-N 0.000 claims description 4
• YXEFNKLNAGUSLQ-UHFFFAOYSA-N 1-[5-[1-[2-(dimethylamino)ethyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CN(CCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C YXEFNKLNAGUSLQ-UHFFFAOYSA-N 0.000 claims description 4
• ZCSYBNDQNSLHCV-UHFFFAOYSA-N 1-[5-[1-[2-hydroxy-3-(4-methoxyphenoxy)propyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)COC1=CC=C(C=C1)OC ZCSYBNDQNSLHCV-UHFFFAOYSA-N 0.000 claims description 4
• YADVXAMMBYQHLC-UHFFFAOYSA-N 1-[5-[3-(1,3-dihydroxypropan-2-yl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCC(CO)C1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C YADVXAMMBYQHLC-UHFFFAOYSA-N 0.000 claims description 4
• RHEFUXIXJKSSIC-UHFFFAOYSA-N 1-[5-[3-(3-hydroxy-3-methylbutyl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C RHEFUXIXJKSSIC-UHFFFAOYSA-N 0.000 claims description 4
• IRRKGXSFAZPFGG-UHFFFAOYSA-N 1-[5-[3-(4,4-difluoropiperidin-2-yl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1(CC(NCC1)C1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)F IRRKGXSFAZPFGG-UHFFFAOYSA-N 0.000 claims description 4
• OGWLTFFSPCXDEN-UHFFFAOYSA-N 1-[5-[3-(6,6-dimethylmorpholin-3-yl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC1(OCC(NC1)C1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C OGWLTFFSPCXDEN-UHFFFAOYSA-N 0.000 claims description 4
• WRWNPDTZJNLWHL-UHFFFAOYSA-N 1-[5-[3-(azetidin-3-yl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N1CC(C1)C1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C WRWNPDTZJNLWHL-UHFFFAOYSA-N 0.000 claims description 4
• PWELIMLHKLTGDL-UHFFFAOYSA-N 1-[5-[3-(cyanomethyl)pyrazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)CC1=NN(C=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C PWELIMLHKLTGDL-UHFFFAOYSA-N 0.000 claims description 4
• CPPTVNDUXDQBLL-FQEVSTJZSA-N 1-[5-[3-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC1(OC[C@H](O1)C1=NOC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C CPPTVNDUXDQBLL-FQEVSTJZSA-N 0.000 claims description 4
• JTOGZPKSNDCQTH-UHFFFAOYSA-N 1-[5-[4-(2-aminoethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C JTOGZPKSNDCQTH-UHFFFAOYSA-N 0.000 claims description 4
• JEBWCAYGOADBSW-UHFFFAOYSA-N 1-[5-[4-(2-cyanoethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C JEBWCAYGOADBSW-UHFFFAOYSA-N 0.000 claims description 4
• WOWSRCBFYWSBCH-UHFFFAOYSA-N 1-[5-[4-(2-hydroxy-2-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(CC)C WOWSRCBFYWSBCH-UHFFFAOYSA-N 0.000 claims description 4
• ASXBLTCWCPLUPP-UHFFFAOYSA-N 1-[5-[4-(2-hydroxy-2-methylpropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C ASXBLTCWCPLUPP-UHFFFAOYSA-N 0.000 claims description 4
• YLHSTXCLJMWIHA-UHFFFAOYSA-N 1-[5-[4-(2-hydroxybutan-2-yl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(C)(CC)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C YLHSTXCLJMWIHA-UHFFFAOYSA-N 0.000 claims description 4
• BNCKJPPMQIMLAL-UHFFFAOYSA-N 1-[5-[4-(2-hydroxybutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CC BNCKJPPMQIMLAL-UHFFFAOYSA-N 0.000 claims description 4
• GDXLYQWXZNXNDM-UHFFFAOYSA-N 1-[5-[4-(2-hydroxyethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C GDXLYQWXZNXNDM-UHFFFAOYSA-N 0.000 claims description 4
• NJDHTBBBXMGCMC-UHFFFAOYSA-N 1-[5-[4-(2-methylpropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C(C)C)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C NJDHTBBBXMGCMC-UHFFFAOYSA-N 0.000 claims description 4
• QVWJJZIWISDYAS-UHFFFAOYSA-N 1-[5-[4-(2-morpholin-4-ylethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCN1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N QVWJJZIWISDYAS-UHFFFAOYSA-N 0.000 claims description 4
• KLZYCKDRZDPTDY-UHFFFAOYSA-N 1-[5-[4-(3,5-dimethoxyphenyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound COC=1C=C(C=C(C=1)OC)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C KLZYCKDRZDPTDY-UHFFFAOYSA-N 0.000 claims description 4
• CQFUXLDLZJTFNZ-UHFFFAOYSA-N 1-[5-[4-(3-aminopropyl)pyrazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCCCC=1C=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C CQFUXLDLZJTFNZ-UHFFFAOYSA-N 0.000 claims description 4
• JBIICBXXSLGLAL-UHFFFAOYSA-N 1-[5-[4-(3-cyanopropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#N)CCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C JBIICBXXSLGLAL-UHFFFAOYSA-N 0.000 claims description 4
• CAMQHKVRNVQNSA-UHFFFAOYSA-N 1-[5-[4-(3-fluoro-3-methylbutyl)triazol-1-yl]-4-(oxetan-3-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC1COC1)(C)C CAMQHKVRNVQNSA-UHFFFAOYSA-N 0.000 claims description 4
• NIDYJZRGTBGNQZ-GOSISDBHSA-N 1-[5-[4-(3-fluoro-3-methylbutyl)triazol-1-yl]-4-[[(3R)-oxolan-3-yl]amino]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)N[C@H]1COCC1)(C)C NIDYJZRGTBGNQZ-GOSISDBHSA-N 0.000 claims description 4
• FIOZNXBIZWGUHJ-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(3,3,3-trifluoropropylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NCCC(F)(F)F)(C)C FIOZNXBIZWGUHJ-UHFFFAOYSA-N 0.000 claims description 4
• QUQQYGRTGFLKDR-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(oxetan-3-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC1COC1)(C)C QUQQYGRTGFLKDR-UHFFFAOYSA-N 0.000 claims description 4
• JXMPVWXEDGELMJ-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C JXMPVWXEDGELMJ-UHFFFAOYSA-N 0.000 claims description 4
• WDYYROXLFPGTIJ-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(propylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NCCC)(C)C WDYYROXLFPGTIJ-UHFFFAOYSA-N 0.000 claims description 4
• RUOXHFNOJLSVFW-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-[(1-methylcyclopropyl)amino]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC1(CC1)C)(C)C RUOXHFNOJLSVFW-UHFFFAOYSA-N 0.000 claims description 4
• KMCYSVDALWYCIE-AWEZNQCLSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-[[(2S)-1-hydroxypropan-2-yl]amino]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)N[C@H](CO)C)(C)C KMCYSVDALWYCIE-AWEZNQCLSA-N 0.000 claims description 4
• DHBSJTRSMVNKQS-UHFFFAOYSA-N 1-[5-[4-(3-hydroxypropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C DHBSJTRSMVNKQS-UHFFFAOYSA-N 0.000 claims description 4
• DRITYCPYJCNBLU-UHFFFAOYSA-N 1-[5-[4-(3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(CC(C)C)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C DRITYCPYJCNBLU-UHFFFAOYSA-N 0.000 claims description 4
• ZPQJZMCOSZSVPI-UHFFFAOYSA-N 1-[5-[4-(3-methylimidazol-4-yl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1=CN=CN1C)N1N=CC=2C1=NC=C(C=2)C#N ZPQJZMCOSZSVPI-UHFFFAOYSA-N 0.000 claims description 4
• VJBQGCHIVPEBHL-UHFFFAOYSA-N 1-[5-[4-(4-hydroxybutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C VJBQGCHIVPEBHL-UHFFFAOYSA-N 0.000 claims description 4
• ZPXBUAUZXWENBV-UHFFFAOYSA-N 1-[5-[4-(aminomethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C ZPXBUAUZXWENBV-UHFFFAOYSA-N 0.000 claims description 4
• UBUOCHKAAOWCSG-UHFFFAOYSA-N 1-[5-[4-(diethylaminomethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)N(CC)CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UBUOCHKAAOWCSG-UHFFFAOYSA-N 0.000 claims description 4
• ZKBYGRZJWHEKKH-UHFFFAOYSA-N 1-[5-[4-(methoxymethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)COC)N1N=CC=2C1=NC=C(C=2)C#N ZKBYGRZJWHEKKH-UHFFFAOYSA-N 0.000 claims description 4
• PUVIMPYGDNXBMU-UHFFFAOYSA-N 1-[5-[4-(methylaminomethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CNC)N1N=CC=2C1=NC=C(C=2)C#N PUVIMPYGDNXBMU-UHFFFAOYSA-N 0.000 claims description 4
• ARLJSZYSATVUIP-UHFFFAOYSA-N 1-[5-[4-(morpholin-4-ylmethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CN1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N ARLJSZYSATVUIP-UHFFFAOYSA-N 0.000 claims description 4
• RMUWYPKKDUJJSH-HSZRJFAPSA-N 1-[5-[4-[(2R)-2-hydroxy-2-phenylethyl]triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H](CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C1=CC=CC=C1 RMUWYPKKDUJJSH-HSZRJFAPSA-N 0.000 claims description 4
• RHROAFKGAHMNEG-QFIPXVFZSA-N 1-[5-[4-[(3S)-3,4-dihydroxy-3-methylbutyl]triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@](CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(CO)C RHROAFKGAHMNEG-QFIPXVFZSA-N 0.000 claims description 4
• LWNOJPJHKZHEHA-UHFFFAOYSA-N 1-[5-[4-[(dimethylamino)methyl]triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CN(C)CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C LWNOJPJHKZHEHA-UHFFFAOYSA-N 0.000 claims description 4
• SWRKUPLIPIEAOS-UHFFFAOYSA-N 1-[5-[4-[1-(2,2-difluoroethyl)piperidin-4-yl]triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1CCC(CC1)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)F SWRKUPLIPIEAOS-UHFFFAOYSA-N 0.000 claims description 4
• FSOWYLCXURDNLF-UHFFFAOYSA-N 1-[5-[5-(3-hydroxy-3-methylbutyl)-1,2-oxazol-3-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CCC1=CC(=NO1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C FSOWYLCXURDNLF-UHFFFAOYSA-N 0.000 claims description 4
• NRGDEORDTOJJIU-NRFANRHFSA-N 1-[5-[5-[(2S)-1-methylsulfonylpiperidin-2-yl]-1,2-oxazol-3-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C1=NOC(=C1)[C@H]1N(CCCC1)S(=O)(=O)C)N1N=CC=2C1=NC=C(C=2)C#N NRGDEORDTOJJIU-NRFANRHFSA-N 0.000 claims description 4
• OQPANNITXUVIRV-UHFFFAOYSA-N 1-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazole-4-carboxamide Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)C(=O)N)NC(C)C OQPANNITXUVIRV-UHFFFAOYSA-N 0.000 claims description 4
• WDTZMRGLHPQLAG-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-5-(1-ethyltriazol-4-yl)-N-propan-2-ylpyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CC WDTZMRGLHPQLAG-UHFFFAOYSA-N 0.000 claims description 4
• QAHXZLFWZUFYLZ-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-5-[1-(3-methylbutyl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC(C)C QAHXZLFWZUFYLZ-UHFFFAOYSA-N 0.000 claims description 4
• MGUVMSUHOVZDJT-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-5-[1-(oxetan-3-yl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C1COC1 MGUVMSUHOVZDJT-UHFFFAOYSA-N 0.000 claims description 4
• FOEMNUAURRCULJ-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-cyclopropyl-5-(1-propyltriazol-4-yl)pyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC1CC1)C=1N=NN(C=1)CCC FOEMNUAURRCULJ-UHFFFAOYSA-N 0.000 claims description 4
• YSRAWZXKTUHGOV-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-propan-2-yl-5-(4-propyltriazol-1-yl)pyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC YSRAWZXKTUHGOV-UHFFFAOYSA-N 0.000 claims description 4
• DXZFLSDIFIFICQ-UHFFFAOYSA-N 2-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]imidazol-1-yl]-N-methylacetamide Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=CN(C=1)CC(=O)NC)NC(C)C DXZFLSDIFIFICQ-UHFFFAOYSA-N 0.000 claims description 4
• LFTXUCLKUQLOES-UHFFFAOYSA-N 2-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]imidazol-1-yl]acetamide Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=CN(C=1)CC(=O)N)NC(C)C LFTXUCLKUQLOES-UHFFFAOYSA-N 0.000 claims description 4
• LIXRHLLKNDMXIL-UHFFFAOYSA-N 3-[4-(cyclopropylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1C=NC=2C1=NC=C(C=2)C#N LIXRHLLKNDMXIL-UHFFFAOYSA-N 0.000 claims description 4
• ASIBBVJMOKFYHG-LBPRGKRZSA-N 3-[4-(ethylamino)-5-[1-[(2S)-2-hydroxypropyl]triazol-4-yl]pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)NC1=CC(=NC=C1C=1N=NN(C=1)C[C@H](C)O)N1C=NC=2C1=NC=C(C=2)C#N ASIBBVJMOKFYHG-LBPRGKRZSA-N 0.000 claims description 4
• HJKMXSZDDUHMHX-UHFFFAOYSA-N 3-[4-(oxetan-3-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound O1CC(C1)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1C=NC=2C1=NC=C(C=2)C#N HJKMXSZDDUHMHX-UHFFFAOYSA-N 0.000 claims description 4
• WRJVYCYDIJCLQP-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1C=NC=2C1=NC=C(C=2)C#N WRJVYCYDIJCLQP-UHFFFAOYSA-N 0.000 claims description 4
• ILKMETLERCAYQP-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1C=NC=2C1=NC=C(C=2)C#N ILKMETLERCAYQP-UHFFFAOYSA-N 0.000 claims description 4
• RLCCLOLGUHLIKZ-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-[1-(3,3,3-trifluoropropyl)triazol-4-yl]pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCC(F)(F)F)N1C=NC=2C1=NC=C(C=2)C#N RLCCLOLGUHLIKZ-UHFFFAOYSA-N 0.000 claims description 4
• TZTOVSFLVLJDJW-UHFFFAOYSA-N 3-[4-[(1-ethylpyrazol-4-yl)amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)N1N=CC(=C1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1C=NC=2C1=NC=C(C=2)C#N TZTOVSFLVLJDJW-UHFFFAOYSA-N 0.000 claims description 4
• LCSLWPXMWNTEBW-CYBMUJFWSA-N 3-[4-[[(2R)-1-hydroxypropan-2-yl]amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC[C@@H](C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1C=NC=2C1=NC=C(C=2)C#N LCSLWPXMWNTEBW-CYBMUJFWSA-N 0.000 claims description 4
• LCSLWPXMWNTEBW-ZDUSSCGKSA-N 3-[4-[[(2S)-1-hydroxypropan-2-yl]amino]-5-(4-propyltriazol-1-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC[C@H](C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1C=NC=2C1=NC=C(C=2)C#N LCSLWPXMWNTEBW-ZDUSSCGKSA-N 0.000 claims description 4
• SWPYUQJPCIWVOY-UHFFFAOYSA-N 3-[4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1C=NC=2C1=NC=C(C=2)C#N)F SWPYUQJPCIWVOY-UHFFFAOYSA-N 0.000 claims description 4
• URGQYYJBXVGVPL-UHFFFAOYSA-N 3-[5-(1-ethyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C URGQYYJBXVGVPL-UHFFFAOYSA-N 0.000 claims description 4
• VJGLHEVDTJZVLY-UHFFFAOYSA-N 3-[5-(1-tert-butyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)(C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C VJGLHEVDTJZVLY-UHFFFAOYSA-N 0.000 claims description 4
• IGSZKLCLZXDOBR-UHFFFAOYSA-N 3-[5-[1-(1-phenylethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C(C)C1=CC=CC=C1)N1C=NC=2C1=NC=C(C=2)C#N IGSZKLCLZXDOBR-UHFFFAOYSA-N 0.000 claims description 4
• RAIFRUPRAVGXCW-UHFFFAOYSA-N 3-[5-[1-(2-hydroxy-2-methylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C RAIFRUPRAVGXCW-UHFFFAOYSA-N 0.000 claims description 4
• OYGKVIABPHELBQ-UHFFFAOYSA-N 3-[5-[1-(3-fluoropropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound FCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C OYGKVIABPHELBQ-UHFFFAOYSA-N 0.000 claims description 4
• ZSQMCXLMTQGSLW-UHFFFAOYSA-N 3-[5-[1-(oxan-4-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CCOCC1)N1C=NC=2C1=NC=C(C=2)C#N ZSQMCXLMTQGSLW-UHFFFAOYSA-N 0.000 claims description 4
• HEOIRVDJQNNTDJ-CYBMUJFWSA-N 3-[5-[1-[(2R)-2-hydroxypropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound O[C@@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)C HEOIRVDJQNNTDJ-CYBMUJFWSA-N 0.000 claims description 4
• HEOIRVDJQNNTDJ-ZDUSSCGKSA-N 3-[5-[1-[(2S)-2-hydroxypropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound O[C@H](CN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)C HEOIRVDJQNNTDJ-ZDUSSCGKSA-N 0.000 claims description 4
• BWWNXTMQXZALHY-UHFFFAOYSA-N 3-[5-[4-(3-hydroxypropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OCCCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C BWWNXTMQXZALHY-UHFFFAOYSA-N 0.000 claims description 4
• LRNOTWMUSIMULG-UHFFFAOYSA-N 3-[5-[4-(methoxymethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)COC)N1C=NC=2C1=NC=C(C=2)C#N LRNOTWMUSIMULG-UHFFFAOYSA-N 0.000 claims description 4
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 4
• FBLYBIUGZFQLRQ-UHFFFAOYSA-N 4-[1-[6-(5-aminopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-ol Chemical compound NC=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)CCC(C)(O)C)NC(C)C FBLYBIUGZFQLRQ-UHFFFAOYSA-N 0.000 claims description 4
• XJGDEKMFWMXXHW-UHFFFAOYSA-N 5-[1-(5-aminopentyl)triazol-4-yl]-N-propan-2-yl-2-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-4-amine Chemical compound NCCCCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=CC2=C1N=CN=C2)NC(C)C XJGDEKMFWMXXHW-UHFFFAOYSA-N 0.000 claims description 4
• JRRBRNNMXNDLDZ-UHFFFAOYSA-N 6-amino-1-[4-(cyclopropylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC1CC1)C=1N=NN(C=1)CCC)C#N JRRBRNNMXNDLDZ-UHFFFAOYSA-N 0.000 claims description 4
• JZDYDRZGPNWULK-UHFFFAOYSA-N 6-amino-1-[4-(oxetan-3-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC1COC1)N1N=NC(=C1)CCC)C#N JZDYDRZGPNWULK-UHFFFAOYSA-N 0.000 claims description 4
• OPHGRSVBCUYHQI-UHFFFAOYSA-N 6-amino-1-[4-(propan-2-ylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC)C#N OPHGRSVBCUYHQI-UHFFFAOYSA-N 0.000 claims description 4
• VIXQFFFOXVRBBD-UHFFFAOYSA-N 6-amino-1-[4-(propan-2-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC)C#N VIXQFFFOXVRBBD-UHFFFAOYSA-N 0.000 claims description 4
• HOFDGKVZXXNSSV-UHFFFAOYSA-N 6-amino-1-[5-(1-cyclohexyltriazol-4-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C1CCCCC1)C#N HOFDGKVZXXNSSV-UHFFFAOYSA-N 0.000 claims description 4
• VZSMXTMRGRXUBF-UHFFFAOYSA-N 6-amino-1-[5-[1-(2-hydroxy-2-methylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CC(C)(C)O)C#N VZSMXTMRGRXUBF-UHFFFAOYSA-N 0.000 claims description 4
• WMTGADPRTSHTMZ-UHFFFAOYSA-N 6-amino-1-[5-[1-(3-fluoropropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCCF)C#N WMTGADPRTSHTMZ-UHFFFAOYSA-N 0.000 claims description 4
• FAVWFPILTBODEE-UHFFFAOYSA-N 6-amino-1-[5-[1-(3-hydroxypropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCCO)C#N FAVWFPILTBODEE-UHFFFAOYSA-N 0.000 claims description 4
• OTVDRBNKDWLPSS-LBPRGKRZSA-N 6-amino-1-[5-[1-[(2S)-2-hydroxypropyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C[C@H](C)O)C#N OTVDRBNKDWLPSS-LBPRGKRZSA-N 0.000 claims description 4
• UWHLQLNUHXFOIX-UHFFFAOYSA-N 6-amino-1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC(C)(C)O)C#N UWHLQLNUHXFOIX-UHFFFAOYSA-N 0.000 claims description 4
• 208000023328 Basedow disease Diseases 0.000 claims description 4
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 208000015023 Graves' disease Diseases 0.000 claims description 4
• 208000003456 Juvenile Arthritis Diseases 0.000 claims description 4
• VLMSQLHYLYKMOF-UHFFFAOYSA-N N-[3-[5-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]-1,2-oxazol-3-yl]propyl]-N-methylacetamide Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C1=CC(=NO1)CCCN(C(C)=O)C)NC(C)C VLMSQLHYLYKMOF-UHFFFAOYSA-N 0.000 claims description 4
• GJEUGALMWHCWLX-UHFFFAOYSA-N N-propan-2-yl-2-pyrazolo[3,4-d]pyrimidin-1-yl-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyridin-4-amine Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)CC(F)(F)F)N1N=CC=2C1=NC=NC=2 GJEUGALMWHCWLX-UHFFFAOYSA-N 0.000 claims description 4
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
• DMHUKEQGRFYIFF-UHFFFAOYSA-N [1-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]methylurea Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)CNC(=O)N)NC(C)C DMHUKEQGRFYIFF-UHFFFAOYSA-N 0.000 claims description 4
• POLZTUCLSKJSPF-UHFFFAOYSA-N [4-[1-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-yl] 2-(dimethylamino)acetate Chemical compound CN(CC(=O)OC(C)(CCC=1N=NN(C=1)C=1C=NC(=CC=1NC(C)C)N1N=CC=2C1=NC=C(C=2)C#N)C)C POLZTUCLSKJSPF-UHFFFAOYSA-N 0.000 claims description 4
• 125000005873 benzo[d]thiazolyl group Chemical group 0.000 claims description 4
• QMZAJEBVYIDVAU-QGZVFWFLSA-N methyl (3R)-3-[5-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]-1,2-oxazol-3-yl]piperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C1=CC(=NO1)[C@H]1CN(CCC1)C(=O)OC)NC(C)C QMZAJEBVYIDVAU-QGZVFWFLSA-N 0.000 claims description 4
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 4
• 150000002825 nitriles Chemical class 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 230000009885 systemic effect Effects 0.000 claims description 4
• ZNPFFFMGECMNPQ-UHFFFAOYSA-N tert-butyl 4-[[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]methyl]-4-hydroxypiperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)CC1(CCN(CC1)C(=O)OC(C)(C)C)O)NC(C)C ZNPFFFMGECMNPQ-UHFFFAOYSA-N 0.000 claims description 4
• 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
• CPLQNQBMMGLAAJ-UHFFFAOYSA-N 1-[5-(4-piperidin-4-yltriazol-1-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1CCNCC1)N1N=CC=2C1=NC=C(C=2)C#N CPLQNQBMMGLAAJ-UHFFFAOYSA-N 0.000 claims description 3
• HAYFLXKGUNUKNH-UHFFFAOYSA-N 1-[5-[1-(1-methylazetidin-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CN(C1)C)N1N=CC=2C1=NC=C(C=2)C#N HAYFLXKGUNUKNH-UHFFFAOYSA-N 0.000 claims description 3
• OAHWJMNKLLUNIB-UHFFFAOYSA-N 1-[5-[1-(2-fluoropropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C OAHWJMNKLLUNIB-UHFFFAOYSA-N 0.000 claims description 3
• QLFRBYIKYRHAIV-UHFFFAOYSA-N 1-[5-[1-(3-methylbutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(CC(C)C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C QLFRBYIKYRHAIV-UHFFFAOYSA-N 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 229910052760 oxygen Inorganic materials 0.000 claims description 3
• 230000000737 periodic effect Effects 0.000 claims description 3
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 2
• OYWJBLUIRUVMEM-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-5-[4-(2-fluoropropyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1N1N=NC(=C1)CC(C)F)N1N=CC=2C1=NC=C(C=2)C#N OYWJBLUIRUVMEM-UHFFFAOYSA-N 0.000 claims description 2
• VOMYPBHBCCYNIK-UHFFFAOYSA-N 1-[4-(cyclopropylamino)-5-[4-(2-hydroxypropyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1N1N=NC(=C1)CC(C)O)N1N=CC=2C1=NC=C(C=2)C#N VOMYPBHBCCYNIK-UHFFFAOYSA-N 0.000 claims description 2
• YAMVDZZOBJPOBX-UHFFFAOYSA-N 1-[5-[1-(2-hydroxy-2-methylbutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(CC)C YAMVDZZOBJPOBX-UHFFFAOYSA-N 0.000 claims description 2
• RZPGFZIWFQTDBE-UHFFFAOYSA-N 1-[5-[1-(2-morpholin-4-ylethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrrolo[2,3-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)CCN1CCOCC1)N1C=CC=2C1=NC=C(C=2)C#N RZPGFZIWFQTDBE-UHFFFAOYSA-N 0.000 claims description 2
• AONABYGFBZESDJ-WOJBJXKFSA-N 1-[5-[1-[(1R,2R)-2-hydroxycyclopentyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]1[C@@H](CCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C AONABYGFBZESDJ-WOJBJXKFSA-N 0.000 claims description 2
• HIHCXVVJXOZCFZ-KGLIPLIRSA-N 1-[5-[1-[(2R,3S)-3-hydroxybutan-2-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]([C@@H](C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C HIHCXVVJXOZCFZ-KGLIPLIRSA-N 0.000 claims description 2
• HIHCXVVJXOZCFZ-KBPBESRZSA-N 1-[5-[1-[(2S,3S)-3-hydroxybutan-2-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H]([C@H](C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C HIHCXVVJXOZCFZ-KBPBESRZSA-N 0.000 claims description 2
• GBYXJRJXGWQDCI-NHCUHLMSSA-N 1-[5-[1-[(3R,4R)-3-hydroxy-1-methylsulfonylpiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H]1CN(CC[C@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)S(=O)(=O)C GBYXJRJXGWQDCI-NHCUHLMSSA-N 0.000 claims description 2
• OMXVXLJKCKINLN-UHFFFAOYSA-N 1-[5-[4-(2-hydroxypropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C OMXVXLJKCKINLN-UHFFFAOYSA-N 0.000 claims description 2
• UVIJIMFLXJXDIZ-UHFFFAOYSA-N 1-[5-[5-(2-hydroxy-2-methylpropyl)-1,2-oxazol-3-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CC1=CC(=NO1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(C)C UVIJIMFLXJXDIZ-UHFFFAOYSA-N 0.000 claims description 2
• LIUUOIUKXULHPC-UHFFFAOYSA-N 3-[5-[1-(2-hydroxy-2-methylbutyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)(CC)C LIUUOIUKXULHPC-UHFFFAOYSA-N 0.000 claims description 2
• LTLPQSZUHQNPKB-UHFFFAOYSA-N 3-[5-[1-(2-hydroxy-3-phenylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C)CC1=CC=CC=C1 LTLPQSZUHQNPKB-UHFFFAOYSA-N 0.000 claims description 2
• LMXFVVSUILIJTN-WOJBJXKFSA-N 3-[5-[1-[(1R,2R)-2-hydroxycyclopentyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound O[C@H]1[C@@H](CCC1)N1N=NC(=C1)C=1C(=CC(=NC=1)N1C=NC=2C1=NC=C(C=2)C#N)NC(C)C LMXFVVSUILIJTN-WOJBJXKFSA-N 0.000 claims description 2
• DGHJKOUXAHNRAP-UHFFFAOYSA-N 4-methyloxadiazole Chemical compound CC1=CON=N1 DGHJKOUXAHNRAP-UHFFFAOYSA-N 0.000 claims description 2
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 claims description 2
• 206010061218 Inflammation Diseases 0.000 claims description 2
• 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
• SDPRMMMKEWXGSX-UHFFFAOYSA-N N-[1-(2,2-difluoroethyl)pyrazol-4-yl]-5-(4-propyltriazol-1-yl)-2-pyrazolo[3,4-d]pyrimidin-1-ylpyridin-4-amine Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1N1N=NC(=C1)CCC)N1N=CC=2C1=NC=NC=2)F SDPRMMMKEWXGSX-UHFFFAOYSA-N 0.000 claims description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 230000004054 inflammatory process Effects 0.000 claims description 2
• 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 208000004296 neuralgia Diseases 0.000 claims description 2
• 208000021722 neuropathic pain Diseases 0.000 claims description 2
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• JSJLRVCRKLICFQ-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(4-pyridin-3-yltriazol-1-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C=1C=NC=CC=1)N1N=CC=2C1=NC=C(C=2)C#N JSJLRVCRKLICFQ-UHFFFAOYSA-N 0.000 claims 2
• CVGBIZKPZLMEAP-UHFFFAOYSA-N 1-[5-(5-morpholin-3-yl-1,2-oxazol-3-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC(C)NC1=CC(=NC=C1C1=NOC(=C1)C1COCCN1)N1N=CC2=C1N=CC(=C2)C#N CVGBIZKPZLMEAP-UHFFFAOYSA-N 0.000 claims 2
• ZTFOXPHCSGLAMA-UHFFFAOYSA-N 1-[5-[1-(2-hydroxy-3-methoxypropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)COC ZTFOXPHCSGLAMA-UHFFFAOYSA-N 0.000 claims 2
• TYLNOBKSOSAELD-UHFFFAOYSA-N 1-[5-[1-(3-ethoxy-2-hydroxypropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)OCC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)O TYLNOBKSOSAELD-UHFFFAOYSA-N 0.000 claims 2
• QZZCGPXUJYOGEJ-UHFFFAOYSA-N 1-[5-[1-[(3-hydroxyoxetan-3-yl)methyl]imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC1(COC1)CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C QZZCGPXUJYOGEJ-UHFFFAOYSA-N 0.000 claims 2
• GBYXJRJXGWQDCI-LEWJYISDSA-N 1-[5-[1-[(3R,4S)-3-hydroxy-1-methylsulfonylpiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H]1CN(CC[C@@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)S(=O)(=O)C GBYXJRJXGWQDCI-LEWJYISDSA-N 0.000 claims 2
• PGGIIIXXQAYLBU-UHFFFAOYSA-N 1-[5-[3-(oxan-4-yl)-1,2-oxazol-5-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C1=CC(=NO1)C1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N PGGIIIXXQAYLBU-UHFFFAOYSA-N 0.000 claims 2
• UYEYUIJZWTVIAP-UHFFFAOYSA-N 1-[5-[4-(2-phenylethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N UYEYUIJZWTVIAP-UHFFFAOYSA-N 0.000 claims 2
• DOQRUHZTCTUYTQ-UHFFFAOYSA-N 1-[5-[4-(3-fluoro-3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-d]pyrimidin-6-amine Chemical compound FC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC(=NC=2)N)NC(C)C)(C)C DOQRUHZTCTUYTQ-UHFFFAOYSA-N 0.000 claims 2
• BNYYPOZIIGWEHG-UHFFFAOYSA-N 1-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-[(1-hydroxy-2-methylpropan-2-yl)amino]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCC(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N BNYYPOZIIGWEHG-UHFFFAOYSA-N 0.000 claims 2
• DUCXLWBEJQZKDI-UHFFFAOYSA-N 1-[5-[5-(morpholine-4-carbonyl)-1,3,4-oxadiazol-2-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1OC(=NN=1)C(=O)N1CCOCC1)N1N=CC=2C1=NC=C(C=2)C#N DUCXLWBEJQZKDI-UHFFFAOYSA-N 0.000 claims 2
• SPYDHZWPENALNF-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-5-[1-(cyclopropylmethyl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CC1CC1 SPYDHZWPENALNF-UHFFFAOYSA-N 0.000 claims 2
• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 claims 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
• 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 claims 2
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims 2
• CAHUMYUYIFWEGM-UHFFFAOYSA-N 1-[4-(ethylamino)-5-[5-(3-hydroxy-3-methylbutyl)-4,5-dihydro-1,2-oxazol-3-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)NC1=CC(=NC=C1C1=NOC(C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N CAHUMYUYIFWEGM-UHFFFAOYSA-N 0.000 claims 1
• OVAMXULYTGDSAK-UHFFFAOYSA-N 1-[5-[1-(oxolan-3-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1COCC1)N1N=CC=2C1=NC=C(C=2)C#N OVAMXULYTGDSAK-UHFFFAOYSA-N 0.000 claims 1
• RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 claims 1
• 102100022691 NACHT, LRR and PYD domains-containing protein 3 Human genes 0.000 claims 1
• 101710126825 NACHT, LRR and PYD domains-containing protein 3 Proteins 0.000 claims 1
• DSJZKVCWSWVJQH-UHFFFAOYSA-N aminomethyl formate Chemical compound NCOC=O DSJZKVCWSWVJQH-UHFFFAOYSA-N 0.000 claims 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
• 125000004928 piperidonyl group Chemical group 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 75
• 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 abstract description 32
• 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 abstract description 16
• 230000002757 inflammatory effect Effects 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 360
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 211
• 239000000203 mixture Chemical class 0.000 description 169
• 235000019439 ethyl acetate Nutrition 0.000 description 161
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 142
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 128
• 239000011541 reaction mixture Substances 0.000 description 120
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 106
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• 238000005481 NMR spectroscopy Methods 0.000 description 94
• 239000000243 solution Substances 0.000 description 92
• 239000000543 intermediate Substances 0.000 description 73
• 239000000047 product Substances 0.000 description 65
• 239000012071 phase Substances 0.000 description 63
• 235000002639 sodium chloride Nutrition 0.000 description 63
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 53
• 238000004128 high performance liquid chromatography Methods 0.000 description 51
• 238000003756 stirring Methods 0.000 description 43
• 238000006243 chemical reaction Methods 0.000 description 42
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
• 238000002360 preparation method Methods 0.000 description 34
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 30
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 239000000725 suspension Substances 0.000 description 29
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 28
• 239000013058 crude material Substances 0.000 description 28
• 206010057190 Respiratory tract infections Diseases 0.000 description 27
• 239000007787 solid Substances 0.000 description 27
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 26
• 239000005695 Ammonium acetate Substances 0.000 description 25
• 235000019257 ammonium acetate Nutrition 0.000 description 25
• 229940043376 ammonium acetate Drugs 0.000 description 25
• 239000011734 sodium Substances 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 239000000460 chlorine Substances 0.000 description 24
• UEWIETUNZIVFLI-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound N#CC1=CN=C2NN=CC2=C1 UEWIETUNZIVFLI-UHFFFAOYSA-N 0.000 description 23
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• 238000002953 preparative HPLC Methods 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 17
• 235000010378 sodium ascorbate Nutrition 0.000 description 17
• 229960005055 sodium ascorbate Drugs 0.000 description 17
• PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• 101710199010 Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 16
• 239000002245 particle Substances 0.000 description 16
• 239000012453 solvate Substances 0.000 description 16
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 14
• 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 13
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 13
• 238000004440 column chromatography Methods 0.000 description 13
• WNEMLSLPVDDDJE-UHFFFAOYSA-N 1-[5-iodo-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound IC=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C WNEMLSLPVDDDJE-UHFFFAOYSA-N 0.000 description 12
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000012267 brine Substances 0.000 description 12
• 239000003153 chemical reaction reagent Substances 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• 239000000651 prodrug Substances 0.000 description 12
• 229940002612 prodrug Drugs 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 239000000463 material Substances 0.000 description 11
• 239000003643 water by type Substances 0.000 description 11
• 241000124008 Mammalia Species 0.000 description 10
• 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 10
• 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 10
• 230000005587 bubbling Effects 0.000 description 10
• 238000005119 centrifugation Methods 0.000 description 10
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 10
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• IMEAUUJJEBOVNT-UHFFFAOYSA-N 2-chloro-5-ethynyl-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C#C IMEAUUJJEBOVNT-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 239000002671 adjuvant Substances 0.000 description 9
• 150000001412 amines Chemical class 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 229910000366 copper(II) sulfate Inorganic materials 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 102000005962 receptors Human genes 0.000 description 9
• 108020003175 receptors Proteins 0.000 description 9
• 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000003995 emulsifying agent Substances 0.000 description 8
• 125000000623 heterocyclic group Chemical group 0.000 description 8
• 239000003755 preservative agent Substances 0.000 description 8
• 230000011664 signaling Effects 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
• 229920000858 Cyclodextrin Polymers 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 235000019441 ethanol Nutrition 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 150000004665 fatty acids Chemical class 0.000 description 7
• 239000000796 flavoring agent Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 102000020233 phosphotransferase Human genes 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 238000000926 separation method Methods 0.000 description 7
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 150000001345 alkine derivatives Chemical class 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 238000001023 centrifugal evaporation Methods 0.000 description 6
• 239000010949 copper Substances 0.000 description 6
• 208000035475 disorder Diseases 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
• 239000000126 substance Substances 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 239000000080 wetting agent Substances 0.000 description 6
• RKBUMNYMWLMGEX-UHFFFAOYSA-N 1-[5-[4-(1-ethylsulfonylpiperidin-4-yl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)S(=O)(=O)N1CCC(CC1)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C RKBUMNYMWLMGEX-UHFFFAOYSA-N 0.000 description 5
• UFEQGUGQPUFFRT-UHFFFAOYSA-N 1-[5-ethynyl-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(#C)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UFEQGUGQPUFFRT-UHFFFAOYSA-N 0.000 description 5
• UZFANXVNOYYZQC-UHFFFAOYSA-N 5-(2,2-difluoroethyl)-1H-pyrazole Chemical compound FC(F)CC1=NNC=C1 UZFANXVNOYYZQC-UHFFFAOYSA-N 0.000 description 5
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
• 206010018634 Gouty Arthritis Diseases 0.000 description 5
• 108091069196 IL-1 family Proteins 0.000 description 5
• 102000039996 IL-1 family Human genes 0.000 description 5
• 229940127590 IRAK4 inhibitor Drugs 0.000 description 5
• 102000000589 Interleukin-1 Human genes 0.000 description 5
• 108010002352 Interleukin-1 Proteins 0.000 description 5
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
• 206010037660 Pyrexia Diseases 0.000 description 5
• 102000002689 Toll-like receptor Human genes 0.000 description 5
• 108020000411 Toll-like receptor Proteins 0.000 description 5
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 229910052802 copper Inorganic materials 0.000 description 5
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 235000013355 food flavoring agent Nutrition 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 208000015181 infectious disease Diseases 0.000 description 5
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
• 239000002609 medium Substances 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 239000003381 stabilizer Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• FJCGXBAKIMNIDC-HTQZYQBOSA-N tert-butyl (3r,4r)-4-azido-3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](N=[N+]=[N-])[C@H](O)C1 FJCGXBAKIMNIDC-HTQZYQBOSA-N 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 4
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
• GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 101000852483 Homo sapiens Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 4
• 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
• 102000019223 Interleukin-1 receptor Human genes 0.000 description 4
• 108050006617 Interleukin-1 receptor Proteins 0.000 description 4
• 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 4
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 4
• 208000034578 Multiple myelomas Diseases 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 208000002193 Pain Diseases 0.000 description 4
• 235000019483 Peanut oil Nutrition 0.000 description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 4
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
• 206010063837 Reperfusion injury Diseases 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• 208000006011 Stroke Diseases 0.000 description 4
• 102100024324 Toll-like receptor 3 Human genes 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 239000003963 antioxidant agent Substances 0.000 description 4
• 235000006708 antioxidants Nutrition 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 239000006227 byproduct Substances 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 238000007872 degassing Methods 0.000 description 4
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
• KWVWELPTVBBQLJ-YUMQZZPRSA-N diazonio-[(3s,4s)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-3-yl]azanide Chemical compound CC(C)(C)OC(=O)N1CC[C@H](O)[C@@H]([N-][N+]#N)C1 KWVWELPTVBBQLJ-YUMQZZPRSA-N 0.000 description 4
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 238000010828 elution Methods 0.000 description 4
• 235000019197 fats Nutrition 0.000 description 4
• 235000003599 food sweetener Nutrition 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 150000004820 halides Chemical class 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
• 208000010125 myocardial infarction Diseases 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 230000036407 pain Effects 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• 239000000312 peanut oil Substances 0.000 description 4
• 229920003023 plastic Polymers 0.000 description 4
• 239000004033 plastic Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 230000002335 preservative effect Effects 0.000 description 4
• 238000010791 quenching Methods 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• ZMNYBXBGSRSANG-DHIUTWEWSA-N tert-butyl (3R,4R)-4-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-hydroxypiperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)O)NC(C)C ZMNYBXBGSRSANG-DHIUTWEWSA-N 0.000 description 4
• 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 150000003852 triazoles Chemical class 0.000 description 4
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 4
• 235000019798 tripotassium phosphate Nutrition 0.000 description 4
• SXVRSCIZJBGJGB-UHFFFAOYSA-N 1-chloropropan-2-ylbenzene Chemical compound ClCC(C)C1=CC=CC=C1 SXVRSCIZJBGJGB-UHFFFAOYSA-N 0.000 description 3
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
• QPVNRFPWQVROHI-UHFFFAOYSA-N 2-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]pyrazol-1-yl]ethanol Chemical compound ClC1=CC(=C(C=N1)C=1C=NN(C=1)CCO)NC(C)C QPVNRFPWQVROHI-UHFFFAOYSA-N 0.000 description 3
• QGSSQOPZQYGFHL-UHFFFAOYSA-N 2-chloro-5-[1-(2-fluoropropyl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CC(C)F QGSSQOPZQYGFHL-UHFFFAOYSA-N 0.000 description 3
• LAWGMJGGUZRERE-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-(4-propyltriazol-1-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC LAWGMJGGUZRERE-UHFFFAOYSA-N 0.000 description 3
• RXLQHELWZLWSCG-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1C=NN(C=1)CC(F)(F)F RXLQHELWZLWSCG-UHFFFAOYSA-N 0.000 description 3
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 3
• BMDQHHCQVNMRCF-UHFFFAOYSA-N 5-[1-(azetidin-3-yl)triazol-4-yl]-2-chloro-N-propan-2-ylpyridin-4-amine Chemical compound N1CC(C1)N1N=NC(=C1)C=1C(=CC(=NC=1)Cl)NC(C)C BMDQHHCQVNMRCF-UHFFFAOYSA-N 0.000 description 3
• UVUUSQHBMMGWEP-UHFFFAOYSA-N 5-azido-2-chloro-N-(3,3-difluorocyclopentyl)pyridin-4-amine Chemical compound N(=[N+]=[N-])C=1C(=CC(=NC=1)Cl)NC1CC(CC1)(F)F UVUUSQHBMMGWEP-UHFFFAOYSA-N 0.000 description 3
• SGCSNJNPPSSPKZ-UHFFFAOYSA-N 5-bromo-2,4-dichloropyridine Chemical compound ClC1=CC(Cl)=C(Br)C=N1 SGCSNJNPPSSPKZ-UHFFFAOYSA-N 0.000 description 3
• YQUMLEDCOBPZNK-UHFFFAOYSA-N 5-bromo-2-chloro-N-propan-2-ylpyridin-4-amine Chemical compound BrC=1C(=CC(=NC=1)Cl)NC(C)C YQUMLEDCOBPZNK-UHFFFAOYSA-N 0.000 description 3
• 244000215068 Acacia senegal Species 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• 201000006474 Brain Ischemia Diseases 0.000 description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 description 3
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 229920000084 Gum arabic Polymers 0.000 description 3
• 206010020751 Hypersensitivity Diseases 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
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 description 3
• 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 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
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 3
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 3
• 102000001253 Protein Kinase Human genes 0.000 description 3
• 206010040047 Sepsis Diseases 0.000 description 3
• 206010040070 Septic Shock Diseases 0.000 description 3
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
• 235000010489 acacia gum Nutrition 0.000 description 3
• 239000000205 acacia gum Substances 0.000 description 3
• 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 3
• 150000001299 aldehydes Chemical class 0.000 description 3
• 208000026935 allergic disease Diseases 0.000 description 3
• 230000002491 angiogenic effect Effects 0.000 description 3
• 230000003078 antioxidant effect Effects 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 150000001540 azides Chemical class 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 206010008118 cerebral infarction Diseases 0.000 description 3
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 3
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
• 125000005805 dimethoxy phenyl group Chemical group 0.000 description 3
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 229910001873 dinitrogen Inorganic materials 0.000 description 3
• NPTVZUXYHNHOJK-UHFFFAOYSA-N ethyl 6-chloro-4-(propan-2-ylamino)pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1NC(C)C NPTVZUXYHNHOJK-UHFFFAOYSA-N 0.000 description 3
• 125000001153 fluoro group Chemical group F* 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 235000010445 lecithin Nutrition 0.000 description 3
• 239000000787 lecithin Substances 0.000 description 3
• 229940067606 lecithin Drugs 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 239000007937 lozenge Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 3
• 208000030159 metabolic disease Diseases 0.000 description 3
• 239000004530 micro-emulsion Substances 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Chemical compound CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
• 239000000346 nonvolatile oil Substances 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 201000008482 osteoarthritis Diseases 0.000 description 3
• 150000002924 oxiranes Chemical class 0.000 description 3
• 239000000123 paper Substances 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
• 229920000053 polysorbate 80 Polymers 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 108060006633 protein kinase Proteins 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 235000015424 sodium Nutrition 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• GVPHIPBSKCVWBA-IAGOWNOFSA-N tert-butyl (3R,4R)-4-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-hydroxypiperidine-1-carboxylate Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)O)NC(C)C GVPHIPBSKCVWBA-IAGOWNOFSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
• JRHPOFJADXHYBR-YUMQZZPRSA-N (1s,2s)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@H]1CCCC[C@@H]1NC JRHPOFJADXHYBR-YUMQZZPRSA-N 0.000 description 2
• DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 2
• FCZKPEQZWDFLAK-CRCLSJGQSA-N (3r,4s)-4-azidopiperidin-3-ol Chemical compound O[C@@H]1CNCC[C@@H]1N=[N+]=[N-] FCZKPEQZWDFLAK-CRCLSJGQSA-N 0.000 description 2
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 2
• WHBOCJQSRORJQN-UHFFFAOYSA-N 1-[(5-bromo-2-chloropyridin-4-yl)amino]-2-methylpropan-2-ol Chemical compound BrC=1C(=CC(=NC=1)Cl)NCC(C)(O)C WHBOCJQSRORJQN-UHFFFAOYSA-N 0.000 description 2
• ACZXPFQRCBSYSV-UHFFFAOYSA-N 1-[3-[4-[6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]azetidin-1-yl]ethanone Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)C1CN(C1)C(C)=O)NC(C)C ACZXPFQRCBSYSV-UHFFFAOYSA-N 0.000 description 2
• WFXUFTVYIODYSW-UHFFFAOYSA-N 1-[4-(propan-2-ylamino)-5-(1-propan-2-yltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C WFXUFTVYIODYSW-UHFFFAOYSA-N 0.000 description 2
• NMOSEHMHSMKNCM-RBUKOAKNSA-N 1-[4-[[(1R,2S)-2-fluorocyclopentyl]amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound F[C@@H]1[C@@H](CCC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N NMOSEHMHSMKNCM-RBUKOAKNSA-N 0.000 description 2
• HDPGEKCXDTWNJW-UHFFFAOYSA-N 1-[4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-5-(1-propyltriazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N)F HDPGEKCXDTWNJW-UHFFFAOYSA-N 0.000 description 2
• IUGJVORUQRSQNZ-UHFFFAOYSA-N 1-[5-(3-piperidin-4-yl-1,2-oxazol-5-yl)-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C1=CC(=NO1)C1CCNCC1)N1N=CC=2C1=NC=C(C=2)C#N IUGJVORUQRSQNZ-UHFFFAOYSA-N 0.000 description 2
• KOBQCUBYLXIFBT-UHFFFAOYSA-N 1-[5-[1-(2-hydroxyethyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OCCN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C KOBQCUBYLXIFBT-UHFFFAOYSA-N 0.000 description 2
• CWDBPSSQTVFNHA-WOJBJXKFSA-N 1-[5-[1-[(3R,4R)-3-hydroxypiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@@H]1CNCC[C@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C CWDBPSSQTVFNHA-WOJBJXKFSA-N 0.000 description 2
• DQIJADHJXLLLQN-UHFFFAOYSA-N 1-[5-[1-[(4-fluorophenyl)methyl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC1=CC=C(CN2N=NC(=C2)C=2C(=CC(=NC=2)N2N=CC=3C2=NC=C(C=3)C#N)NC(C)C)C=C1 DQIJADHJXLLLQN-UHFFFAOYSA-N 0.000 description 2
• AITZXVLIDDMWAO-UHFFFAOYSA-N 1-[5-[4-(1-methylsulfonylpiperidin-4-yl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)C1CCN(CC1)S(=O)(=O)C)N1N=CC=2C1=NC=C(C=2)C#N AITZXVLIDDMWAO-UHFFFAOYSA-N 0.000 description 2
• UGDBUTSCGFDAAN-UHFFFAOYSA-N 1-[5-[4-(2-hydroxypropan-2-yl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(C)(C)C=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C UGDBUTSCGFDAAN-UHFFFAOYSA-N 0.000 description 2
• BDZSNCUWWQIVLW-UHFFFAOYSA-N 1-[5-[4-(phenylsulfanylmethyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CSC1=CC=CC=C1)N1N=CC=2C1=NC=C(C=2)C#N BDZSNCUWWQIVLW-UHFFFAOYSA-N 0.000 description 2
• RHROAFKGAHMNEG-JOCHJYFZSA-N 1-[5-[4-[(3R)-3,4-dihydroxy-3-methylbutyl]triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@](CCC=1N=NN(C=1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)(CO)C RHROAFKGAHMNEG-JOCHJYFZSA-N 0.000 description 2
• XGYUOXNSWJCBTG-UHFFFAOYSA-N 1-[[2-chloro-5-[4-(2-hydroxypropyl)triazol-1-yl]pyridin-4-yl]amino]-2-methylpropan-2-ol Chemical compound ClC1=NC=C(C(=C1)NCC(C)(O)C)N1N=NC(=C1)CC(C)O XGYUOXNSWJCBTG-UHFFFAOYSA-N 0.000 description 2
• OSYOXHTVSHZPRO-UHFFFAOYSA-N 1-azido-3-methylbutane Chemical compound CC(C)CCN=[N+]=[N-] OSYOXHTVSHZPRO-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 2
• RKRYCXRYSCMHIY-UHFFFAOYSA-N 2-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-propan-2-yl-5-(1-propyltriazol-4-yl)pyridin-4-amine Chemical compound ClC=1C=C2C(=NC=1)N(N=C2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC RKRYCXRYSCMHIY-UHFFFAOYSA-N 0.000 description 2
• APOMDYFFDBMPEL-UHFFFAOYSA-N 2-chloro-5-(1-methyltriazol-4-yl)-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C APOMDYFFDBMPEL-UHFFFAOYSA-N 0.000 description 2
• ZEZIQKHQAIDTBC-UHFFFAOYSA-N 2-chloro-5-[1-(1-methylazetidin-3-yl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)C1CN(C1)C ZEZIQKHQAIDTBC-UHFFFAOYSA-N 0.000 description 2
• ITBVVAJUXWACRD-UHFFFAOYSA-N 2-chloro-5-[1-(3-methylbutyl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC(C)C ITBVVAJUXWACRD-UHFFFAOYSA-N 0.000 description 2
• CLUIEZOGBBVHSO-UHFFFAOYSA-N 2-chloro-5-iodo-n-propan-2-ylpyridin-4-amine Chemical compound CC(C)NC1=CC(Cl)=NC=C1I CLUIEZOGBBVHSO-UHFFFAOYSA-N 0.000 description 2
• DEJUUKULVAIMNF-UHFFFAOYSA-N 2-chloro-5-iodopyridin-4-amine Chemical compound NC1=CC(Cl)=NC=C1I DEJUUKULVAIMNF-UHFFFAOYSA-N 0.000 description 2
• UFEDAUAQHDAJKG-UHFFFAOYSA-N 2-chloro-N-(3,3-difluorocyclopentyl)-5-nitropyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC1CC(CC1)(F)F)[N+](=O)[O-] UFEDAUAQHDAJKG-UHFFFAOYSA-N 0.000 description 2
• TWPMAZAGQGSEKT-UHFFFAOYSA-N 2-chloro-N-[1-(2,2-difluoroethyl)pyrazol-4-yl]-5-(1-propylpyrazol-4-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC=1C=NN(C=1)CC(F)F)C=1C=NN(C=1)CCC TWPMAZAGQGSEKT-UHFFFAOYSA-N 0.000 description 2
• UOHZRXFHKPIJQH-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-(1-propyltriazol-4-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC UOHZRXFHKPIJQH-UHFFFAOYSA-N 0.000 description 2
• ZRJCNMYMCUBLAI-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-(1H-pyrazol-4-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1C=NNC=1 ZRJCNMYMCUBLAI-UHFFFAOYSA-N 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• SDJXIZMGMOVUNA-UHFFFAOYSA-N 3-fluoro-2-methylhex-5-yn-2-ol Chemical compound FC(C(C)(O)C)CC#C SDJXIZMGMOVUNA-UHFFFAOYSA-N 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 2
• AUTZOIIGOKGLNM-UHFFFAOYSA-N 5-(2,2-dibromoethenyl)-N-propan-2-yl-2-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-4-amine Chemical compound BrC(=CC=1C(=CC(=NC=1)N1C=CC2=C1N=CN=C2)NC(C)C)Br AUTZOIIGOKGLNM-UHFFFAOYSA-N 0.000 description 2
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 2
• OJYCMVQQWGSGBY-UHFFFAOYSA-N 5-bromo-2-chloro-N-[1-(2,2-difluoroethyl)pyrazol-4-yl]pyridin-4-amine Chemical compound BrC=1C(=CC(=NC=1)Cl)NC=1C=NN(C=1)CC(F)F OJYCMVQQWGSGBY-UHFFFAOYSA-N 0.000 description 2
• RQPURORIQIJXNJ-UHFFFAOYSA-N 5-ethynyl-N-propan-2-yl-2-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-4-amine Chemical compound C(#C)C=1C(=CC(=NC=1)N1C=CC2=C1N=CN=C2)NC(C)C RQPURORIQIJXNJ-UHFFFAOYSA-N 0.000 description 2
• TWPJYDAPOSJMRF-UHFFFAOYSA-N 6-chloro-4-N-(3,3-difluorocyclopentyl)pyridine-3,4-diamine Chemical compound ClC1=CC(=C(C=N1)N)NC1CC(CC1)(F)F TWPJYDAPOSJMRF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 208000006386 Bone Resorption Diseases 0.000 description 2
• BCXIWUQVXKPTAQ-UHFFFAOYSA-N C(CC)N1C=NC(=C1)[Sn](CCCC)(CCCC)CCCC Chemical compound C(CC)N1C=NC(=C1)[Sn](CCCC)(CCCC)CCCC BCXIWUQVXKPTAQ-UHFFFAOYSA-N 0.000 description 2
• AJDUFGPZEKPRSU-AOOOYVTPSA-N CC(C)(C)OC(=O)N[C@H]1CC[C@@H](OS(C)(=O)=O)CC1 Chemical compound CC(C)(C)OC(=O)N[C@H]1CC[C@@H](OS(C)(=O)=O)CC1 AJDUFGPZEKPRSU-AOOOYVTPSA-N 0.000 description 2
• 206010006895 Cachexia Diseases 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 2
• 208000031886 HIV Infections Diseases 0.000 description 2
• 208000037357 HIV infectious disease Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000852255 Homo sapiens Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 description 2
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 102100036433 Interleukin-1 receptor-associated kinase-like 2 Human genes 0.000 description 2
• 239000005909 Kieselgur Substances 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 208000001132 Osteoporosis Diseases 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• 201000011152 Pemphigus Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 208000004880 Polyuria Diseases 0.000 description 2
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
• CIRITGBVSKUMAF-ZDUSSCGKSA-N [(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropyl] methanesulfonate Chemical compound CC(C)(C)OC(=O)N[C@H](COS(C)(=O)=O)CC1=CC=CC=C1 CIRITGBVSKUMAF-ZDUSSCGKSA-N 0.000 description 2
• ACCYPTJWYUDZSB-UHFFFAOYSA-N [4-[1-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-yl] cyclopropanecarboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)N1N=NC(=C1)CCC(C)(C)OC(=O)C1CC1)NC(C)C ACCYPTJWYUDZSB-UHFFFAOYSA-N 0.000 description 2
• DBDQQUWTCJIGTQ-UHFFFAOYSA-N [6-chloro-4-(propan-2-ylamino)pyridin-3-yl]methanol Chemical compound CC(C)NC1=CC(Cl)=NC=C1CO DBDQQUWTCJIGTQ-UHFFFAOYSA-N 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000012082 adaptor molecule Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 230000002238 attenuated effect Effects 0.000 description 2
• 201000004982 autoimmune uveitis Diseases 0.000 description 2
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
• 229960004853 betadex Drugs 0.000 description 2
• 230000024279 bone resorption Effects 0.000 description 2
• FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 2
• NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 208000001969 capillary hemangioma Diseases 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000011111 cardboard Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 229940097362 cyclodextrins Drugs 0.000 description 2
• 229960004397 cyclophosphamide Drugs 0.000 description 2
• 208000001763 cytomegalovirus retinitis Diseases 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000007783 downstream signaling Effects 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• HFPARSSPAQXOAL-UHFFFAOYSA-N ethyl 2-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]pyrazol-1-yl]acetate Chemical compound ClC1=CC(=C(C=N1)C=1C=NN(C=1)CC(=O)OCC)NC(C)C HFPARSSPAQXOAL-UHFFFAOYSA-N 0.000 description 2
• NOEFIUWJGDCTGB-UHFFFAOYSA-N ethyl 4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridine-3-carboxylate Chemical compound C(C)(C)NC1=CC(=NC=C1C(=O)OCC)N1C=CC2=C1N=CN=C2 NOEFIUWJGDCTGB-UHFFFAOYSA-N 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000003292 glue Substances 0.000 description 2
• 229960002706 gusperimus Drugs 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 239000006166 lysate Substances 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 208000021039 metastatic melanoma Diseases 0.000 description 2
• QEAMVPPRBXKVDC-UHFFFAOYSA-N methyl 2-fluoropent-4-ynoate Chemical compound FC(C(=O)OC)CC#C QEAMVPPRBXKVDC-UHFFFAOYSA-N 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 2
• IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• 201000001976 pemphigus vulgaris Diseases 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 102000013415 peroxidase activity proteins Human genes 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 229940127557 pharmaceutical product Drugs 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
• 239000008389 polyethoxylated castor oil Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• HDMGAZBPFLDBCX-UHFFFAOYSA-M potassium;sulfooxy sulfate Chemical compound [K+].OS(=O)(=O)OOS([O-])(=O)=O HDMGAZBPFLDBCX-UHFFFAOYSA-M 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 229910052707 ruthenium Inorganic materials 0.000 description 2
• 231100000241 scar Toxicity 0.000 description 2
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229960004793 sucrose Drugs 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• NVMDJZFOHJJHKK-UHFFFAOYSA-N tert-butyl 4-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-fluoropiperidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)C1C(CN(CC1)C(=O)OC(C)(C)C)F)NC(C)C NVMDJZFOHJJHKK-UHFFFAOYSA-N 0.000 description 2
• FGCDEYWWGHBADH-DEOSSOPVSA-N tert-butyl N-[(2S)-1-[4-[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-phenylpropan-2-yl]carbamate Chemical compound C(#N)C=1C=C2C(=NC=1)N(N=C2)C1=CC(=C(C=N1)C=1N=NN(C=1)C[C@H](CC1=CC=CC=C1)NC(OC(C)(C)C)=O)NC(C)C FGCDEYWWGHBADH-DEOSSOPVSA-N 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 2
• 229960000984 tocofersolan Drugs 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 230000008736 traumatic injury Effects 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
• 230000002485 urinary effect Effects 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• 239000002076 α-tocopherol Substances 0.000 description 2
• 235000004835 α-tocopherol Nutrition 0.000 description 2
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• VMFCTZUYOILUMY-UHFFFAOYSA-N 1,1-difluoro-2-iodoethane Chemical compound FC(F)CI VMFCTZUYOILUMY-UHFFFAOYSA-N 0.000 description 1
• 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• 125000006091 1,3-dioxolane group Chemical group 0.000 description 1
• LMAYRTOWGOVCOR-UHFFFAOYSA-N 1-(2,2-difluoroethyl)pyrazol-4-amine Chemical compound NC=1C=NN(CC(F)F)C=1 LMAYRTOWGOVCOR-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
• AHZPVHVTSSSRMJ-UHFFFAOYSA-N 1-[3-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]azetidin-1-yl]ethanone Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)C1CN(C1)C(C)=O)NC(C)C AHZPVHVTSSSRMJ-UHFFFAOYSA-N 0.000 description 1
• WBPYPIADDKSQDR-UHFFFAOYSA-N 1-[4-(2,2-difluoroethylamino)-5-[5-(3-hydroxy-3-methylbutyl)-4,5-dihydro-1,2-oxazol-3-yl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CNC1=CC(=NC=C1C1=NOC(C1)CCC(C)(C)O)N1N=CC=2C1=NC=C(C=2)C#N)F WBPYPIADDKSQDR-UHFFFAOYSA-N 0.000 description 1
• KLPCSOBVJZSKIT-UHFFFAOYSA-N 1-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-2-methylpropan-2-ol Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)CC(C)(O)C)NC(C)C KLPCSOBVJZSKIT-UHFFFAOYSA-N 0.000 description 1
• AEALZTZDRZHKKK-UHFFFAOYSA-N 1-[4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-5-(1-propylpyrazol-4-yl)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1C=1C=NN(C=1)CCC)N1N=CC=2C1=NC=C(C=2)C#N)F AEALZTZDRZHKKK-UHFFFAOYSA-N 0.000 description 1
• FHJATBIERQTCTN-UHFFFAOYSA-N 1-[4-amino-2-(ethylaminomethyl)imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol Chemical compound C1=CC=CC2=C(N(C(CNCC)=N3)CC(C)(C)O)C3=C(N)N=C21 FHJATBIERQTCTN-UHFFFAOYSA-N 0.000 description 1
• JQTLPOGPBQUVKP-UHFFFAOYSA-N 1-[5-[1-(2-hydroxy-3-phenylpropyl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound OC(CN1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)CC1=CC=CC=C1 JQTLPOGPBQUVKP-UHFFFAOYSA-N 0.000 description 1
• HWUDIBHSVZRJER-AWEZNQCLSA-N 1-[5-[1-[(2S)-2-hydroxypropyl]imidazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound O[C@H](CN1C=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C)C HWUDIBHSVZRJER-AWEZNQCLSA-N 0.000 description 1
• QCYBEIUZSYEGNW-XLIONFOSSA-N 1-[5-[1-[(3R,4S)-3-fluoropiperidin-4-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound F[C@@H]1CNCC[C@@H]1N1N=NC(=C1)C=1C(=CC(=NC=1)N1N=CC=2C1=NC=C(C=2)C#N)NC(C)C QCYBEIUZSYEGNW-XLIONFOSSA-N 0.000 description 1
• MKNBSVXIVJQKEE-UHFFFAOYSA-N 1-[5-[1-[1-(2,2-difluoroethyl)azetidin-3-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound CC(C)NC1=CC(=NC=C1C1=CN(N=N1)C1CN(CC(F)F)C1)N1N=CC2=C1N=CC(=C2)C#N MKNBSVXIVJQKEE-UHFFFAOYSA-N 0.000 description 1
• BFKKIDHWWRDAPL-UHFFFAOYSA-N 1-[5-[1-[1-(5-methyl-1,3,4-oxadiazol-2-yl)azetidin-3-yl]triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CN(C1)C=1OC(=NN=1)C)N1N=CC=2C1=NC=C(C=2)C#N BFKKIDHWWRDAPL-UHFFFAOYSA-N 0.000 description 1
• HRZKBJFQSQYJPJ-UHFFFAOYSA-N 1-[5-[4-(2-oxopropyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CC(C)=O)N1N=CC=2C1=NC=C(C=2)C#N HRZKBJFQSQYJPJ-UHFFFAOYSA-N 0.000 description 1
• LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 1
• PVHDFPXDDFJTRQ-UHFFFAOYSA-N 1-azido-11,11-dimethyldodecane Chemical compound CC(CCCCCCCCCCN=[N+]=[N-])(C)C PVHDFPXDDFJTRQ-UHFFFAOYSA-N 0.000 description 1
• AGCPPSNKHQEFRX-UHFFFAOYSA-N 1-azidoethanol Chemical compound CC(O)N=[N+]=[N-] AGCPPSNKHQEFRX-UHFFFAOYSA-N 0.000 description 1
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
• BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 1
• IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 1
• VPLXJIGDEIRJLV-UHFFFAOYSA-N 12,12-dimethyltridec-1-yne Chemical group CC(CCCCCCCCCC#C)(C)C VPLXJIGDEIRJLV-UHFFFAOYSA-N 0.000 description 1
• JSJVFFWMERFSLW-UHFFFAOYSA-N 1H-pyridin-2-one 1H-pyrrole Chemical compound N1C(C=CC=C1)=O.N1C=CC=C1 JSJVFFWMERFSLW-UHFFFAOYSA-N 0.000 description 1
• OZYNGTUTZIFTBW-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridine-6-carbonitrile Chemical compound N#CC1=CN=C2N=CNC2=C1 OZYNGTUTZIFTBW-UHFFFAOYSA-N 0.000 description 1
• QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
• DRAQIXNADYAISI-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-5-carbonitrile Chemical compound N#CC1=CN=C2NC=CC2=C1 DRAQIXNADYAISI-UHFFFAOYSA-N 0.000 description 1
• RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
• FJRPOHLDJUJARI-UHFFFAOYSA-N 2,3-dihydro-1,2-oxazole Chemical compound C1NOC=C1 FJRPOHLDJUJARI-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• RZVJQUMDJUUBBF-UHFFFAOYSA-N 2,4-dichloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C=C1Cl RZVJQUMDJUUBBF-UHFFFAOYSA-N 0.000 description 1
• YVQFZSHMTCZYMI-UHFFFAOYSA-N 2-(1h-pyrazol-4-yl)ethanol Chemical compound OCCC=1C=NNC=1 YVQFZSHMTCZYMI-UHFFFAOYSA-N 0.000 description 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
• BYVMKCHHWASQFN-UHFFFAOYSA-N 2-chloro-3-iodopyridin-4-amine Chemical compound NC1=CC=NC(Cl)=C1I BYVMKCHHWASQFN-UHFFFAOYSA-N 0.000 description 1
• RDCALBLDTSOITP-UHFFFAOYSA-N 2-chloro-5-[1-(2-morpholin-4-ylethyl)triazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical group ClC1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCN1CCOCC1 RDCALBLDTSOITP-UHFFFAOYSA-N 0.000 description 1
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
• KECLBWRZPDPNHF-UHFFFAOYSA-N 2-chloro-N-cyclopropyl-5-ethynylpyridin-4-amine Chemical group ClC1=NC=C(C(=C1)NC1CC1)C#C KECLBWRZPDPNHF-UHFFFAOYSA-N 0.000 description 1
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
• HBDIAYVNLDXHSZ-UHFFFAOYSA-N 2-methylhex-5-yn-2-ol Chemical compound CC(C)(O)CCC#C HBDIAYVNLDXHSZ-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• ZPFUWAVLEWIOEJ-UHFFFAOYSA-N 2-nitropyridin-4-amine Chemical compound NC1=CC=NC([N+]([O-])=O)=C1 ZPFUWAVLEWIOEJ-UHFFFAOYSA-N 0.000 description 1
• DMMLYMQQBZGHLO-UHFFFAOYSA-N 2-propan-2-ylpyridin-4-amine Chemical compound CC(C)C1=CC(N)=CC=N1 DMMLYMQQBZGHLO-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• QLOHXGYAULHFOG-UHFFFAOYSA-N 3,3-difluorocyclopentan-1-amine Chemical compound NC1CCC(F)(F)C1 QLOHXGYAULHFOG-UHFFFAOYSA-N 0.000 description 1
• JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
• XEMDFESAXKSEGI-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CN=C1 XEMDFESAXKSEGI-UHFFFAOYSA-N 0.000 description 1
• IEDRUQXJIWTVIL-UHFFFAOYSA-N 3-(bromomethyl)oxetane Chemical compound BrCC1COC1 IEDRUQXJIWTVIL-UHFFFAOYSA-N 0.000 description 1
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
• ZPEBAEKERPMXKR-UHFFFAOYSA-N 3-bromopropyl(tert-butyl)carbamic acid Chemical group CC(C)(C)N(C(O)=O)CCCBr ZPEBAEKERPMXKR-UHFFFAOYSA-N 0.000 description 1
• BKNDBCLJFUKLAQ-UHFFFAOYSA-N 3-ethynylpyridin-4-amine Chemical compound NC1=CC=NC=C1C#C BKNDBCLJFUKLAQ-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• VWPXSWMYEMPJGB-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC(F)(F)F)N=C1 VWPXSWMYEMPJGB-UHFFFAOYSA-N 0.000 description 1
• BLBDTBCGPHPIJK-UHFFFAOYSA-N 4-Amino-2-chloropyridine Chemical compound NC1=CC=NC(Cl)=C1 BLBDTBCGPHPIJK-UHFFFAOYSA-N 0.000 description 1
• GJBTUVXFTJVKLY-UHFFFAOYSA-N 4-[1-[6-chloro-4-[(3,3-difluorocyclopentyl)amino]pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-ol Chemical compound ClC1=CC(=C(C=N1)N1N=NC(=C1)CCC(C)(O)C)NC1CC(CC1)(F)F GJBTUVXFTJVKLY-UHFFFAOYSA-N 0.000 description 1
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
• DLHAWERXBUJHNY-UHFFFAOYSA-N 4-benzyl-1h-pyrazole Chemical compound C=1C=CC=CC=1CC=1C=NNC=1 DLHAWERXBUJHNY-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• QUCCWHGGHCTFJS-UHFFFAOYSA-N 4-iodo-1-propylimidazole Chemical compound CCCN1C=NC(I)=C1 QUCCWHGGHCTFJS-UHFFFAOYSA-N 0.000 description 1
• RETRFRCRQVNKKD-UHFFFAOYSA-N 5-(2-bromoethynyl)-N-propan-2-yl-2-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-4-amine Chemical compound BrC#CC=1C(=CC(=NC=1)N1C=CC2=C1N=CN=C2)NC(C)C RETRFRCRQVNKKD-UHFFFAOYSA-N 0.000 description 1
• KTMQQKMLYDWDKL-UHFFFAOYSA-N 5-chloro-1h-pyrazolo[3,4-b]pyridine Chemical compound ClC1=CN=C2NN=CC2=C1 KTMQQKMLYDWDKL-UHFFFAOYSA-N 0.000 description 1
• MJFZDRIOIJLJRF-UHFFFAOYSA-N 6-chloro-4-(propan-2-ylamino)pyridine-3-carbaldehyde Chemical compound CC(C)NC1=CC(Cl)=NC=C1C=O MJFZDRIOIJLJRF-UHFFFAOYSA-N 0.000 description 1
• AULWPXHFRBLPAE-UHFFFAOYSA-N 6-chloropyridine Chemical compound ClC1=C=CC=C[N]1 AULWPXHFRBLPAE-UHFFFAOYSA-N 0.000 description 1
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
• 108010011485 Aspartame Proteins 0.000 description 1
• 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
• 208000004429 Bacillary Dysentery Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
• PYCRDFAOWGKPKT-UHFFFAOYSA-N C(C)C1=C(C(=C(C=C1)I)OCC)CC Chemical compound C(C)C1=C(C(=C(C=C1)I)OCC)CC PYCRDFAOWGKPKT-UHFFFAOYSA-N 0.000 description 1
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• JFDPMTSQEGGYFQ-UHFFFAOYSA-N CCCC[Sn](CCCC)(CCCC)C1=NC=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 JFDPMTSQEGGYFQ-UHFFFAOYSA-N 0.000 description 1
• 102000004631 Calcineurin Human genes 0.000 description 1
• 108010042955 Calcineurin Proteins 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 206010063094 Cerebral malaria Diseases 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 206010008909 Chronic Hepatitis Diseases 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 206010012438 Dermatitis atopic 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
• 241000196324 Embryophyta Species 0.000 description 1
• 206010014561 Emphysema Diseases 0.000 description 1
• 208000037487 Endotoxemia Diseases 0.000 description 1
• 241000713730 Equine infectious anemia virus Species 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 239000001116 FEMA 4028 Substances 0.000 description 1
• 241000713800 Feline immunodeficiency virus Species 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 239000001828 Gelatine Substances 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 206010019755 Hepatitis chronic active Diseases 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
• ZMFQAGDZRKITDR-UHFFFAOYSA-N IN=CC(CC)=N Chemical compound IN=CC(CC)=N ZMFQAGDZRKITDR-UHFFFAOYSA-N 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 206010061598 Immunodeficiency Diseases 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 102000003814 Interleukin-10 Human genes 0.000 description 1
• 108090000174 Interleukin-10 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical class CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 206010028289 Muscle atrophy Diseases 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
• ONUGPELGXPYXKW-UHFFFAOYSA-N NNCCC1CC1.Cl Chemical compound NNCCC1CC1.Cl ONUGPELGXPYXKW-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 102000042894 Pelle family Human genes 0.000 description 1
• 108091082316 Pelle family Proteins 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 206010038997 Retroviral infections Diseases 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• GOOHAUXETOMSMM-VKHMYHEASA-N S-propylene oxide Chemical compound C[C@H]1CO1 GOOHAUXETOMSMM-VKHMYHEASA-N 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• 206010040550 Shigella infections Diseases 0.000 description 1
• 201000010001 Silicosis Diseases 0.000 description 1
• 208000004346 Smoldering Multiple Myeloma Diseases 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
• 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
• 239000004809 Teflon Substances 0.000 description 1
• 229920006362 Teflon® Polymers 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 244000299461 Theobroma cacao Species 0.000 description 1
• 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
• 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 206010043781 Thyroiditis chronic Diseases 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 206010048873 Traumatic arthritis Diseases 0.000 description 1
• GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
• 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• SOQBYJOCHVBHJO-VIFPVBQESA-N [(2S)-1-azido-3-phenylpropan-2-yl]carbamic acid Chemical compound N(=[N+]=[N-])C[C@H](CC1=CC=CC=C1)NC(O)=O SOQBYJOCHVBHJO-VIFPVBQESA-N 0.000 description 1
• RIVZZXPIBAGRCN-UHFFFAOYSA-N [4-(propan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridin-3-yl]methanol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1C=CC2=C1N=CN=C2)CO RIVZZXPIBAGRCN-UHFFFAOYSA-N 0.000 description 1
• YBICQFHOKGEYFL-UHFFFAOYSA-N [6-(5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl)-4-(propan-2-ylamino)pyridin-3-yl]methanol Chemical compound C(C)(C)NC1=C(C=NC(=C1)N1CCC2=C1N=CN=C2)CO YBICQFHOKGEYFL-UHFFFAOYSA-N 0.000 description 1
• DCUBASOTLJXLQS-UHFFFAOYSA-L [O-]C(=O)CCCCCCCCC.OC(=O)CCCCCCCCC.[O-]C(=O)CCCCCCCCC.[Mg+2] Chemical compound [O-]C(=O)CCCCCCCCC.OC(=O)CCCCCCCCC.[O-]C(=O)CCCCCCCCC.[Mg+2] DCUBASOTLJXLQS-UHFFFAOYSA-L 0.000 description 1
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
• 229960004748 abacavir Drugs 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 150000004075 acetic anhydrides Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 230000004721 adaptive immunity Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002390 adhesive tape Substances 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 229940087168 alpha tocopherol Drugs 0.000 description 1
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
• 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 230000036592 analgesia Effects 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000003430 antimalarial agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 201000005000 autoimmune gastritis Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 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 1
• 230000000903 blocking effect Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• UNXISIRQWPTTSN-UHFFFAOYSA-N boron;2,3-dimethylbutane-2,3-diol Chemical compound [B].[B].CC(C)(O)C(C)(C)O UNXISIRQWPTTSN-UHFFFAOYSA-N 0.000 description 1
• 239000006189 buccal tablet Substances 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 235000001046 cacaotero Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
• 229960000590 celecoxib Drugs 0.000 description 1
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
• 229910000420 cerium oxide Inorganic materials 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000007810 chemical reaction solvent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• NMMPMZWIIQCZBA-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;2-phenylethanamine Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 NMMPMZWIIQCZBA-UHFFFAOYSA-M 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 238000011284 combination treatment Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
• KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
• GCFAUZGWPDYAJN-UHFFFAOYSA-N cyclohexyl 3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1C=CC(=O)OC1CCCCC1 GCFAUZGWPDYAJN-UHFFFAOYSA-N 0.000 description 1
• 150000001942 cyclopropanes Chemical class 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• ZVXHZSXYHFBIEW-UHFFFAOYSA-N dimethyl 2-fluoropropanedioate Chemical compound COC(=O)C(F)C(=O)OC ZVXHZSXYHFBIEW-UHFFFAOYSA-N 0.000 description 1
• FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 208000016097 disease of metabolism Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 1
• AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 1
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
• 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
• NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
• 229950004696 flusalan Drugs 0.000 description 1
• 230000004907 flux Effects 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
• 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229940075529 glyceryl stearate Drugs 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 208000005252 hepatitis A Diseases 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
• ATBKVKDEMSGMTQ-UHFFFAOYSA-N hydrazine triphenylphosphane Chemical compound NN.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 ATBKVKDEMSGMTQ-UHFFFAOYSA-N 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
• 229960004171 hydroxychloroquine Drugs 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000007813 immunodeficiency 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
• 239000012535 impurity Substances 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
• 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
• 229940076144 interleukin-10 Drugs 0.000 description 1
• 230000004068 intracellular signaling Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 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
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000003866 lung sarcoma Diseases 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000007721 medicinal effect Effects 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• CWOWIOGLWARZNY-UHFFFAOYSA-N methyl 6-methyl-7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical group C1N(C(=O)OC)CCC2OC21C CWOWIOGLWARZNY-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 239000000693 micelle Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• 229940043348 myristyl alcohol Drugs 0.000 description 1
• 229950006780 n-acetylglucosamine Drugs 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([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
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 238000006384 oligomerization reaction Methods 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000001151 other effect Effects 0.000 description 1
• DWYJHMSKXMHOAP-UHFFFAOYSA-N oxetan-2-ol Chemical compound OC1CCO1 DWYJHMSKXMHOAP-UHFFFAOYSA-N 0.000 description 1
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 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
• 239000012188 paraffin wax Substances 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• JTHLRRZARWSHBE-UHFFFAOYSA-N pent-4-yn-2-ol Chemical compound CC(O)CC#C JTHLRRZARWSHBE-UHFFFAOYSA-N 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 208000008494 pericarditis Diseases 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229910003446 platinum oxide Inorganic materials 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 229940072288 prograf Drugs 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• HXKVNRKJSSHQQY-UHFFFAOYSA-N prop-2-ynylsulfanylbenzene Chemical compound C#CCSC1=CC=CC=C1 HXKVNRKJSSHQQY-UHFFFAOYSA-N 0.000 description 1
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
• 125000006308 propyl amino group Chemical group 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 239000013014 purified material Substances 0.000 description 1
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
• 150000003254 radicals Chemical group 0.000 description 1
• 229940099538 rapamune Drugs 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000250 revascularization Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
• 229950005741 rolipram Drugs 0.000 description 1
• 201000005404 rubella Diseases 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 150000003902 salicylic acid esters Chemical class 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 208000015891 sexual disease Diseases 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 201000005113 shigellosis Diseases 0.000 description 1
• 208000010721 smoldering plasma cell myeloma Diseases 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 230000007928 solubilization Effects 0.000 description 1
• 238000005063 solubilization Methods 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 239000008347 soybean phospholipid Substances 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 229910000080 stannane Inorganic materials 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
• 238000004808 supercritical fluid chromatography Methods 0.000 description 1
• 201000004595 synovitis Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 229960001967 tacrolimus Drugs 0.000 description 1
• LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
• 229960003676 tenidap Drugs 0.000 description 1
• HRLUZSSGBKDEGK-QMMMGPOBSA-N tert-butyl (2s)-2-(azidomethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CN=[N+]=[N-] HRLUZSSGBKDEGK-QMMMGPOBSA-N 0.000 description 1
• GVPHIPBSKCVWBA-DLBZAZTESA-N tert-butyl (3R,4S)-4-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-hydroxypiperidine-1-carboxylate Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)[C@@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)O)NC(C)C GVPHIPBSKCVWBA-DLBZAZTESA-N 0.000 description 1
• KWVWELPTVBBQLJ-HTQZYQBOSA-N tert-butyl (3r,4r)-3-azido-4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](O)[C@H](N=[N+]=[N-])C1 KWVWELPTVBBQLJ-HTQZYQBOSA-N 0.000 description 1
• XTDXZSGSIMLARD-UHFFFAOYSA-N tert-butyl 2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC=CC=C1 XTDXZSGSIMLARD-UHFFFAOYSA-N 0.000 description 1
• ZHQJKBCCOFSQEM-UHFFFAOYSA-N tert-butyl 3-azidoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N=[N+]=[N-])C1 ZHQJKBCCOFSQEM-UHFFFAOYSA-N 0.000 description 1
• UOQFEIVQXBUGTL-UHFFFAOYSA-N tert-butyl 4-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-fluoropiperidine-1-carboxylate Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)C1C(CN(CC1)C(=O)OC(C)(C)C)F)NC(C)C UOQFEIVQXBUGTL-UHFFFAOYSA-N 0.000 description 1
• MMPWHAJQEZIIEH-UHFFFAOYSA-N tert-butyl 7-oxa-4-azabicyclo[4.1.0]heptane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2OC21 MMPWHAJQEZIIEH-UHFFFAOYSA-N 0.000 description 1
• FTJPFAQZUZRSKY-UHFFFAOYSA-N tert-butyl N-(2-bromoethylamino)carbamate Chemical compound BrCCNNC(OC(C)(C)C)=O FTJPFAQZUZRSKY-UHFFFAOYSA-N 0.000 description 1
• PAMORZHZCRBLTD-UHFFFAOYSA-N tert-butyl N-(butan-2-ylamino)carbamate Chemical compound CCC(C)NNC(=O)OC(C)(C)C PAMORZHZCRBLTD-UHFFFAOYSA-N 0.000 description 1
• UMBXYHRYEHEXSL-SFHVURJKSA-N tert-butyl N-[(2S)-1-[4-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]triazol-1-yl]-3-phenylpropan-2-yl]carbamate Chemical compound ClC1=CC(=C(C=N1)C=1N=NN(C=1)C[C@H](CC1=CC=CC=C1)NC(OC(C)(C)C)=O)NC(C)C UMBXYHRYEHEXSL-SFHVURJKSA-N 0.000 description 1
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
• IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 1
• LDKDMDVMMCXTMO-GFCCVEGCSA-N tert-butyl n-[(2r)-1-hydroxy-3-phenylpropan-2-yl]carbamate Chemical group CC(C)(C)OC(=O)N[C@@H](CO)CC1=CC=CC=C1 LDKDMDVMMCXTMO-GFCCVEGCSA-N 0.000 description 1
• GTAVEQBEFSJELB-LBPRGKRZSA-N tert-butyl n-[(2s)-1-azido-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CN=[N+]=[N-])CC1=CC=CC=C1 GTAVEQBEFSJELB-LBPRGKRZSA-N 0.000 description 1
• LDKDMDVMMCXTMO-LBPRGKRZSA-N tert-butyl n-[(2s)-1-hydroxy-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)CC1=CC=CC=C1 LDKDMDVMMCXTMO-LBPRGKRZSA-N 0.000 description 1
• LPQZERIRKRYGGM-UHFFFAOYSA-N tert-butyl pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1 LPQZERIRKRYGGM-UHFFFAOYSA-N 0.000 description 1
• 108091008743 testicular receptors 4 Proteins 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 230000009772 tissue formation Effects 0.000 description 1
• 208000004371 toothache Diseases 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000012070 whole genome sequencing analysis Methods 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1