BRPI0713328A2 - derivados de piridina e pirazina como inibidores de cinase mnk - Google Patents

Info

Publication number

BRPI0713328A2

BRPI0713328A2 BRPI0713328-6A BRPI0713328A BRPI0713328A2 BR PI0713328 A2 BRPI0713328 A2 BR PI0713328A2 BR PI0713328 A BRPI0713328 A BR PI0713328A BR PI0713328 A2 BRPI0713328 A2 BR PI0713328A2

Authority

BR

Brazil

Prior art keywords

pyrazin

alkyl

indol

amino

mmol

Prior art date

2006-06-22

Links

• Espacenet
• Global Dossier
• Discuss

• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title abstract description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 title abstract description 5
• 229940043355 kinase inhibitor Drugs 0.000 title abstract description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 3
• 150000003216 pyrazines Chemical class 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 336
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 58
• 208000035475 disorder Diseases 0.000 claims abstract description 50
• 238000011282 treatment Methods 0.000 claims abstract description 48
• 101710139011 MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 claims abstract description 38
• 102100026299 MAP kinase-interacting serine/threonine-protein kinase 1 Human genes 0.000 claims abstract description 38
• 101710138999 MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims abstract description 28
• 102100033610 MAP kinase-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims abstract description 27
• 238000011321 prophylaxis Methods 0.000 claims abstract description 27
• 230000000694 effects Effects 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 230000002596 correlated effect Effects 0.000 claims abstract description 12
• 239000003814 drug Substances 0.000 claims abstract description 10
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 288
• -1 aminocarbonylphenyl Chemical group 0.000 claims description 276
• 238000000034 method Methods 0.000 claims description 244
• 125000000217 alkyl group Chemical group 0.000 claims description 77
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 76
• 125000000623 heterocyclic group Chemical group 0.000 claims description 69
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 63
• 150000003839 salts Chemical class 0.000 claims description 52
• 125000001424 substituent group Chemical group 0.000 claims description 41
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 35
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 25
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
• 239000000651 prodrug Chemical group 0.000 claims description 22
• 229940002612 prodrug Drugs 0.000 claims description 22
• 206010028980 Neoplasm Diseases 0.000 claims description 21
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 19
• 125000005842 heteroatom Chemical group 0.000 claims description 18
• 125000001041 indolyl group Chemical group 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 125000002252 acyl group Chemical group 0.000 claims description 16
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 16
• 201000011510 cancer Diseases 0.000 claims description 16
• 206010012601 diabetes mellitus Diseases 0.000 claims description 15
• 208000008589 Obesity Diseases 0.000 claims description 14
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 14
• 230000004968 inflammatory condition Effects 0.000 claims description 14
• 235000020824 obesity Nutrition 0.000 claims description 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
• 241000124008 Mammalia Species 0.000 claims description 11
• 150000001204 N-oxides Chemical group 0.000 claims description 11
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 11
• 230000003287 optical effect Effects 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
• XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 claims description 10
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 9
• 230000037396 body weight Effects 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 150000004677 hydrates Chemical class 0.000 claims description 9
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
• 201000008482 osteoarthritis Diseases 0.000 claims description 8
• 206010006895 Cachexia Diseases 0.000 claims description 7
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 7
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 7
• 206010020772 Hypertension Diseases 0.000 claims description 7
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 7
• 208000029078 coronary artery disease Diseases 0.000 claims description 7
• 229910052739 hydrogen Inorganic materials 0.000 claims description 7
• 201000002859 sleep apnea Diseases 0.000 claims description 7
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 201000001421 hyperglycemia Diseases 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 208000030814 Eating disease Diseases 0.000 claims description 5
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
• 235000014632 disordered eating Nutrition 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 210000000232 gallbladder Anatomy 0.000 claims description 4
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 201000001883 cholelithiasis Diseases 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 208000001130 gallstones Diseases 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
• PKUBWSRLUOHNPZ-UHFFFAOYSA-N 3-fluoro-5-[6-(6-fluoro-1h-indol-2-yl)pyrazin-2-yl]-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C(F)=CC(C=2N=C(C=NC=2)C=2NC3=CC(F)=CC=C3C=2)=CC=1C(=O)N(C)C1CCN(C)C1 PKUBWSRLUOHNPZ-UHFFFAOYSA-N 0.000 claims description 2
• XMTXOOYCGUDHQX-UHFFFAOYSA-N 3-methoxy-n-methyl-4-[[6-(6-methyl-1h-indol-2-yl)pyrazin-2-yl]amino]-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC(C)=CC=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 XMTXOOYCGUDHQX-UHFFFAOYSA-N 0.000 claims description 2
• OGSUUHVBRCGZAU-UHFFFAOYSA-N 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-n-(2,3-dihydroxypropyl)benzamide Chemical compound N1=C(C=2OC3=CC=CC=C3C=2)C(N)=NC=C1C1=CC=C(C(=O)NCC(O)CO)C=C1 OGSUUHVBRCGZAU-UHFFFAOYSA-N 0.000 claims description 2
• HJANIWAXHMBUSG-UHFFFAOYSA-N 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-n-[3-[bis(2-hydroxyethyl)amino]propyl]benzamide Chemical compound N1=C(C=2OC3=CC=CC=C3C=2)C(N)=NC=C1C1=CC=C(C(=O)NCCCN(CCO)CCO)C=C1 HJANIWAXHMBUSG-UHFFFAOYSA-N 0.000 claims description 2
• LANXWFYAJDTUQO-UHFFFAOYSA-N 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-n-ethyl-n-(2-hydroxyethyl)benzamide Chemical compound C1=CC(C(=O)N(CCO)CC)=CC=C1C1=CN=C(N)C(C=2OC3=CC=CC=C3C=2)=N1 LANXWFYAJDTUQO-UHFFFAOYSA-N 0.000 claims description 2
• PNZKKQWBSPXAPD-UHFFFAOYSA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 PNZKKQWBSPXAPD-UHFFFAOYSA-N 0.000 claims description 2
• CGPRHVRLWRCWJA-UHFFFAOYSA-N 4-[[6-(4-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC(F)=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 CGPRHVRLWRCWJA-UHFFFAOYSA-N 0.000 claims description 2
• GBTXJILKTQBTQO-UHFFFAOYSA-N 4-[[6-(6-chloro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC(Cl)=CC=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 GBTXJILKTQBTQO-UHFFFAOYSA-N 0.000 claims description 2
• RCOTZFFXLPZDMS-GOSISDBHSA-N [(3r)-3-(dimethylamino)pyrrolidin-1-yl]-[3-methoxy-4-[[6-(1h-pyrrolo[3,2-c]pyridin-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=NC=C3C=2)C(OC)=CC=1C(=O)N1CC[C@@H](N(C)C)C1 RCOTZFFXLPZDMS-GOSISDBHSA-N 0.000 claims description 2
• XLWQOGPOLMFUFI-CALCHBBNSA-N [(3r,5s)-3,5-dimethylpiperazin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1C[C@H](C)N[C@H](C)C1 XLWQOGPOLMFUFI-CALCHBBNSA-N 0.000 claims description 2
• LHFZSYIZPPCJQA-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCC(N(C)C)C1 LHFZSYIZPPCJQA-UHFFFAOYSA-N 0.000 claims description 2
• LIZCVZCUXNDWID-UHFFFAOYSA-N [4-(2-hydroxyethyl)piperazin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCN(CCO)CC1 LIZCVZCUXNDWID-UHFFFAOYSA-N 0.000 claims description 2
• CMTPWEJEADPAFJ-OAHLLOKOSA-N [4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-[(3r)-3-methylpiperazin-1-yl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CCN[C@H](C)C1 CMTPWEJEADPAFJ-OAHLLOKOSA-N 0.000 claims description 2
• VNHSDZLHPCFUJV-UHFFFAOYSA-N [6-[[5-(5-fluoro-1h-indol-2-yl)pyridin-3-yl]amino]pyridin-3-yl]-piperazin-1-ylmethanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(C=1)=CN=CC=1NC(N=C1)=CC=C1C(=O)N1CCNCC1 VNHSDZLHPCFUJV-UHFFFAOYSA-N 0.000 claims description 2
• FVKBASVXAYEXPY-UHFFFAOYSA-N acetic acid;4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]benzamide Chemical compound CC(O)=O.C1=CC(C(=O)N)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 FVKBASVXAYEXPY-UHFFFAOYSA-N 0.000 claims description 2
• IRDCGQYTXLOSOM-UHFFFAOYSA-N acetic acid;[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-morpholin-4-ylmethanone Chemical compound CC(O)=O.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C=CC=1C(=O)N1CCOCC1 IRDCGQYTXLOSOM-UHFFFAOYSA-N 0.000 claims description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
• FQNVEWSIRAAFDY-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-4-[6-(1h-indol-2-yl)pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)NCC(O)CO)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 FQNVEWSIRAAFDY-UHFFFAOYSA-N 0.000 claims description 2
• FQNVEWSIRAAFDY-KRWDZBQOSA-N n-[(2s)-2,3-dihydroxypropyl]-4-[6-(1h-indol-2-yl)pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)NC[C@H](O)CO)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 FQNVEWSIRAAFDY-KRWDZBQOSA-N 0.000 claims description 2
• QEHZTXHMFSBBQW-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methylbenzamide Chemical compound COC1=CC(C(=O)N(C)CCN(C)C)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 QEHZTXHMFSBBQW-UHFFFAOYSA-N 0.000 claims description 2
• KRAFXUXYGUZYOZ-UHFFFAOYSA-N n-ethyl-n-(2-hydroxyethyl)-4-[6-(1h-indol-2-yl)pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)N(CCO)CC)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 KRAFXUXYGUZYOZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
• IHYDKONBGFJEEL-UHFFFAOYSA-N tert-butyl 3-[[[4-[6-(1h-indol-2-yl)pyrazin-2-yl]benzoyl]amino]methyl]piperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1CNC(=O)C1=CC=C(C=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C=C1 IHYDKONBGFJEEL-UHFFFAOYSA-N 0.000 claims description 2
• YDUPFVYOLHJSGF-UHFFFAOYSA-N tert-butyl n-[1-[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzoyl]azetidin-3-yl]carbamate Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CC(NC(=O)OC(C)(C)C)C1 YDUPFVYOLHJSGF-UHFFFAOYSA-N 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
• 125000003282 alkyl amino group Chemical group 0.000 claims 3
• IPBNVTMTIKJPSK-UHFFFAOYSA-N (3-aminoazetidin-1-yl)-[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CC(N)C1 IPBNVTMTIKJPSK-UHFFFAOYSA-N 0.000 claims 1
• XCUZPVBDBASDCD-UHFFFAOYSA-N 2,9-diazaspiro[4.5]decan-2-yl-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N(C1)CCC21CCCNC2 XCUZPVBDBASDCD-UHFFFAOYSA-N 0.000 claims 1
• FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims 1
• GMDXKZWRGGYIIL-UHFFFAOYSA-N 2-[6-[4-(4-methylpiperazine-1-carbonyl)anilino]pyrazin-2-yl]-1h-indole-5-carboxamide Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CC=C(C=C3C=2)C(N)=O)=N1 GMDXKZWRGGYIIL-UHFFFAOYSA-N 0.000 claims 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims 1
• UNUXUUBNCRXUMH-UHFFFAOYSA-N 3-methoxy-n-methyl-4-[[6-(5-methyl-1h-indol-2-yl)pyrazin-2-yl]amino]-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(C)C=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 UNUXUUBNCRXUMH-UHFFFAOYSA-N 0.000 claims 1
• ZRZOSUIBWQOEGM-UHFFFAOYSA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-piperidin-3-ylbenzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)NC1CCCNC1 ZRZOSUIBWQOEGM-UHFFFAOYSA-N 0.000 claims 1
• ZJPPAUXADIFCJC-UHFFFAOYSA-N 4-[[6-(5-chloro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(Cl)C=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 ZJPPAUXADIFCJC-UHFFFAOYSA-N 0.000 claims 1
• PLYJSWZGCPGSCQ-UHFFFAOYSA-N 4-[[6-(5-cyano-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(C=C3C=2)C#N)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 PLYJSWZGCPGSCQ-UHFFFAOYSA-N 0.000 claims 1
• NWLPGLSOMDEYCD-UHFFFAOYSA-N 4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 NWLPGLSOMDEYCD-UHFFFAOYSA-N 0.000 claims 1
• KFNNXOYZKPSREJ-UHFFFAOYSA-N 4-[[6-(6-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC(F)=CC=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 KFNNXOYZKPSREJ-UHFFFAOYSA-N 0.000 claims 1
• QDBWBNDBUKEGSC-UHFFFAOYSA-N 4-[[6-(7-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=C(F)C=CC=C3C=2)C(OC)=CC=1C(=O)N(C)C1CCN(C)C1 QDBWBNDBUKEGSC-UHFFFAOYSA-N 0.000 claims 1
• DDIIYGHHUMKDGI-UHFFFAOYSA-N 5-fluoro-1,3-dihydroindol-2-one Chemical compound FC1=CC=C2NC(=O)CC2=C1 DDIIYGHHUMKDGI-UHFFFAOYSA-N 0.000 claims 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
• VMGFCBXBANWBPC-LJQANCHMSA-N [(3r)-3-(dimethylamino)pyrrolidin-1-yl]-[3-methoxy-4-[[6-(6-methoxy-1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound N1C2=CC(OC)=CC=C2C=C1C(N=1)=CN=CC=1NC(C(=C1)OC)=CC=C1C(=O)N1CC[C@@H](N(C)C)C1 VMGFCBXBANWBPC-LJQANCHMSA-N 0.000 claims 1
• AHAWPPZIBXCDSQ-HXUWFJFHSA-N [(3r)-3-(dimethylamino)pyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound C1[C@H](N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 AHAWPPZIBXCDSQ-HXUWFJFHSA-N 0.000 claims 1
• YSJOQWCLLYPLTQ-QGZVFWFLSA-N [(3r)-3-aminopyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CC[C@@H](N)C1 YSJOQWCLLYPLTQ-QGZVFWFLSA-N 0.000 claims 1
• ONYIMVNCXQKHJT-QGZVFWFLSA-N [(3r)-3-aminopyrrolidin-1-yl]-[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CC[C@@H](N)C1 ONYIMVNCXQKHJT-QGZVFWFLSA-N 0.000 claims 1
• AHAWPPZIBXCDSQ-FQEVSTJZSA-N [(3s)-3-(dimethylamino)pyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound C1[C@@H](N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 AHAWPPZIBXCDSQ-FQEVSTJZSA-N 0.000 claims 1
• YSJOQWCLLYPLTQ-KRWDZBQOSA-N [(3s)-3-aminopyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CC[C@H](N)C1 YSJOQWCLLYPLTQ-KRWDZBQOSA-N 0.000 claims 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
• MEQAZNGFRKGLQN-UHFFFAOYSA-N [2-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone Chemical compound ClC1=CC(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)=CC=C1C(=O)N1CCNCC1 MEQAZNGFRKGLQN-UHFFFAOYSA-N 0.000 claims 1
• ARBYDFNSZUAGKQ-UHFFFAOYSA-N [3-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(Cl)=CC=1C(=O)N1CCNCC1 ARBYDFNSZUAGKQ-UHFFFAOYSA-N 0.000 claims 1
• KUIRMWHHKSNSTJ-UHFFFAOYSA-N [3-methoxy-4-[[6-(6-methoxy-1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone Chemical compound N1C2=CC(OC)=CC=C2C=C1C(N=1)=CN=CC=1NC(C(=C1)OC)=CC=C1C(=O)N1CCNCC1 KUIRMWHHKSNSTJ-UHFFFAOYSA-N 0.000 claims 1
• LJCCJXHEPSIOPN-UHFFFAOYSA-N [4-[3-(dimethylamino)propyl]piperazin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-2-methoxyphenyl]methanone Chemical compound COC1=CC(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)=CC=C1C(=O)N1CCN(CCCN(C)C)CC1 LJCCJXHEPSIOPN-UHFFFAOYSA-N 0.000 claims 1
• ZIVCXJIWLIRETL-UHFFFAOYSA-N [4-[5-(1h-indol-2-yl)pyridin-3-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C=2C=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C=CC=1C(=O)N1CCOCC1 ZIVCXJIWLIRETL-UHFFFAOYSA-N 0.000 claims 1
• YCHVWRYIYRLCEF-UHFFFAOYSA-N [4-[6-(6-methyl-1h-indol-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound N1C2=CC(C)=CC=C2C=C1C(N=1)=CN=CC=1C(C=C1)=CC=C1C(=O)N1CCOCC1 YCHVWRYIYRLCEF-UHFFFAOYSA-N 0.000 claims 1
• VREHNJGXNKBGFR-UHFFFAOYSA-N [4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCN(C)CC1 VREHNJGXNKBGFR-UHFFFAOYSA-N 0.000 claims 1
• QMKQGTZXNUZQKC-UHFFFAOYSA-N [4-[[6-(4-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-piperazin-1-ylmethanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC(F)=C3C=2)C(OC)=CC=1C(=O)N1CCNCC1 QMKQGTZXNUZQKC-UHFFFAOYSA-N 0.000 claims 1
• LUMYNPZLRZBLQF-UHFFFAOYSA-N [5-chloro-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-2-methoxyphenyl]-piperazin-1-ylmethanone Chemical compound COC1=CC(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)=C(Cl)C=C1C(=O)N1CCNCC1 LUMYNPZLRZBLQF-UHFFFAOYSA-N 0.000 claims 1
• UONRFQNJFBKWEB-UHFFFAOYSA-N [6-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]pyridin-3-yl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound C1CN(C)CCCN1C(=O)C(C=N1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 UONRFQNJFBKWEB-UHFFFAOYSA-N 0.000 claims 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
• PHEQIDUACUIYEG-UHFFFAOYSA-N n-(1,2-diethylpyrazolidin-4-yl)-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound C1N(CC)N(CC)CC1NC(=O)C(C=C1OC)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 PHEQIDUACUIYEG-UHFFFAOYSA-N 0.000 claims 1
• QFDRBXUQNMKNAH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-4-[5-(1h-indol-2-yl)pyridin-3-yl]benzamide Chemical compound C1=CC(C(=O)NCCN(CC)CC)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=C1 QFDRBXUQNMKNAH-UHFFFAOYSA-N 0.000 claims 1
• VTNHHYGXQQBHGX-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCCN(C)C)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 VTNHHYGXQQBHGX-UHFFFAOYSA-N 0.000 claims 1
• BPRBMHIBHVTUIE-UHFFFAOYSA-N tert-butyl 3-[[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzoyl]amino]azetidine-1-carboxylate Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)NC1CN(C(=O)OC(C)(C)C)C1 BPRBMHIBHVTUIE-UHFFFAOYSA-N 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 12
• 239000003112 inhibitor Substances 0.000 abstract description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 296
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 294
• 239000000203 mixture Substances 0.000 description 190
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
• 238000002953 preparative HPLC Methods 0.000 description 177
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
• 239000000543 intermediate Substances 0.000 description 137
• 239000007787 solid Substances 0.000 description 131
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 113
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 102
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
• 239000007921 spray Substances 0.000 description 95
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
• 239000000047 product Substances 0.000 description 90
• 235000019439 ethyl acetate Nutrition 0.000 description 82
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 77
• 239000013058 crude material Substances 0.000 description 76
• 239000012317 TBTU Substances 0.000 description 73
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 73
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 70
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 64
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 56
• 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 56
• 235000017557 sodium bicarbonate Nutrition 0.000 description 51
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 51
• 239000002904 solvent Substances 0.000 description 51
• 238000005160 1H NMR spectroscopy Methods 0.000 description 49
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 48
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 46
• 239000002253 acid Substances 0.000 description 45
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 43
• 238000000746 purification Methods 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 41
• 239000000243 solution Substances 0.000 description 40
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 39
• 239000012043 crude product Substances 0.000 description 37
• 238000005481 NMR spectroscopy Methods 0.000 description 34
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 34
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 34
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 34
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 33
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 32
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 32
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 32
• 239000012071 phase Substances 0.000 description 32
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 31
• 239000011734 sodium Substances 0.000 description 31
• 239000012074 organic phase Substances 0.000 description 30
• 239000000463 material Substances 0.000 description 29
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
• 230000002829 reductive effect Effects 0.000 description 27
• 239000012044 organic layer Substances 0.000 description 25
• 241000400611 Eucalyptus deanei Species 0.000 description 24
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 24
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 23
• 239000005711 Benzoic acid Substances 0.000 description 22
• 239000008346 aqueous phase Substances 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 229910052763 palladium Inorganic materials 0.000 description 21
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 21
• LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 20
• 150000001412 amines Chemical class 0.000 description 20
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 20
• 229960003742 phenol Drugs 0.000 description 19
• 230000002441 reversible effect Effects 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 17
• 238000001914 filtration Methods 0.000 description 17
• 102000004877 Insulin Human genes 0.000 description 16
• 108090001061 Insulin Proteins 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 16
• 229940125396 insulin Drugs 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• RMOKKNQYJXNDHH-UHFFFAOYSA-N 5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl RMOKKNQYJXNDHH-UHFFFAOYSA-N 0.000 description 15
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 14
• 241000282414 Homo sapiens Species 0.000 description 13
• 238000007792 addition Methods 0.000 description 13
• 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 12
• QPMSBFJPIQPFEZ-UHFFFAOYSA-N 4-(6-chloropyrazin-2-yl)phenol Chemical compound C1=CC(O)=CC=C1C1=CN=CC(Cl)=N1 QPMSBFJPIQPFEZ-UHFFFAOYSA-N 0.000 description 12
• 108091054455 MAP kinase family Proteins 0.000 description 12
• 102000043136 MAP kinase family Human genes 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• 238000004007 reversed phase HPLC Methods 0.000 description 12
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 11
• 108091000080 Phosphotransferase Proteins 0.000 description 11
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 11
• PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 11
• 235000010233 benzoic acid Nutrition 0.000 description 11
• 102000020233 phosphotransferase Human genes 0.000 description 11
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 11
• 238000005507 spraying Methods 0.000 description 11
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
• 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 10
• 101150003085 Pdcl gene Proteins 0.000 description 10
• 239000008103 glucose Substances 0.000 description 10
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 10
• UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 10
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
• HPFBOMPHLMXHRE-UHFFFAOYSA-N 4-[(6-chloropyrazin-2-yl)amino]-3-methoxy-n-methyl-n-(1-methylpyrrolidin-3-yl)benzamide Chemical compound COC1=CC(C(=O)N(C)C2CN(C)CC2)=CC=C1NC1=CN=CC(Cl)=N1 HPFBOMPHLMXHRE-UHFFFAOYSA-N 0.000 description 9
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 9
• 206010039491 Sarcoma Diseases 0.000 description 9
• 230000014509 gene expression Effects 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• CZGIEJXGCLWRPY-UHFFFAOYSA-N n,1-dimethylpyrrolidin-3-amine Chemical compound CNC1CCN(C)C1 CZGIEJXGCLWRPY-UHFFFAOYSA-N 0.000 description 9
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 8
• OGLQQIYCIMAPLI-UHFFFAOYSA-N 3-methoxy-4-[[6-[1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]pyrazin-2-yl]amino]benzoic acid Chemical class COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2N(C3=CC=CC=C3C=2)C(=O)OC(C)(C)C)=N1 OGLQQIYCIMAPLI-UHFFFAOYSA-N 0.000 description 8
• PFWWDFZZHQTJJN-UHFFFAOYSA-N 4-(3-amino-6-bromopyrazin-2-yl)phenol Chemical compound NC1=NC=C(Br)N=C1C1=CC=C(O)C=C1 PFWWDFZZHQTJJN-UHFFFAOYSA-N 0.000 description 8
• LNGDCOBXAXHNCD-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 LNGDCOBXAXHNCD-UHFFFAOYSA-N 0.000 description 8
• 206010025323 Lymphomas Diseases 0.000 description 8
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 208000009956 adenocarcinoma Diseases 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 8
• XIUGHPCLAKRSLE-UHFFFAOYSA-N 4-[(6-chloropyrazin-2-yl)amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(Cl)=N1 XIUGHPCLAKRSLE-UHFFFAOYSA-N 0.000 description 7
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
• 150000001413 amino acids Chemical class 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000008569 process Effects 0.000 description 7
• 150000003222 pyridines Chemical class 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• URICCAHIKKRPTN-UHFFFAOYSA-N 3-chloro-4-[(6-chloropyrazin-2-yl)amino]benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1NC1=CN=CC(Cl)=N1 URICCAHIKKRPTN-UHFFFAOYSA-N 0.000 description 6
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 6
• 201000009030 Carcinoma Diseases 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• 238000006069 Suzuki reaction reaction Methods 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 6
• SVIBPSNFXYUOFT-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 SVIBPSNFXYUOFT-UHFFFAOYSA-N 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
• DTLBKXRFWUERQN-UHFFFAOYSA-N 3,5-dibromopyrazin-2-amine Chemical class NC1=NC=C(Br)N=C1Br DTLBKXRFWUERQN-UHFFFAOYSA-N 0.000 description 5
• XIDYQTQPRALPDL-UHFFFAOYSA-N 3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 XIDYQTQPRALPDL-UHFFFAOYSA-N 0.000 description 5
• BOFHWWUKWDIWLG-UHFFFAOYSA-N 3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 BOFHWWUKWDIWLG-UHFFFAOYSA-N 0.000 description 5
• PCNLELUQYXJVOO-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 PCNLELUQYXJVOO-UHFFFAOYSA-N 0.000 description 5
• YIYBPEDZAUFQLO-UHFFFAOYSA-N 4-amino-3-chlorobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1Cl YIYBPEDZAUFQLO-UHFFFAOYSA-N 0.000 description 5
• RPRQXRNAKBLLIB-UHFFFAOYSA-N 4-chloro-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 RPRQXRNAKBLLIB-UHFFFAOYSA-N 0.000 description 5
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 229910002666 PdCl2 Inorganic materials 0.000 description 5
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 5
• 108091005682 Receptor kinases Proteins 0.000 description 5
• TZHYEXHDCFQZGG-UHFFFAOYSA-N [5-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound FC1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 TZHYEXHDCFQZGG-UHFFFAOYSA-N 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 239000003480 eluent Substances 0.000 description 5
• 150000002430 hydrocarbons Chemical class 0.000 description 5
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 206010041823 squamous cell carcinoma Diseases 0.000 description 5
• 230000001629 suppression Effects 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 4
• YIHXTTJVWOFGKY-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,2$l^{5},4$l^{5},6$l^{5}-dioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)CP(=O)(CCC)OP(=O)(CCC)O1 YIHXTTJVWOFGKY-UHFFFAOYSA-N 0.000 description 4
• CYHFSMDWDNUHAF-UHFFFAOYSA-N 2-(6-chloropyrazin-2-yl)-5-fluoro-1h-indole Chemical compound C=1C2=CC(F)=CC=C2NC=1C1=CN=CC(Cl)=N1 CYHFSMDWDNUHAF-UHFFFAOYSA-N 0.000 description 4
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
• WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 4
• ORNOIUNHNRPDCW-UHFFFAOYSA-N 3-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 ORNOIUNHNRPDCW-UHFFFAOYSA-N 0.000 description 4
• QKZUTMIQZDIZMR-UHFFFAOYSA-N 4-[(6-chloropyrazin-2-yl)amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=CN=CC(Cl)=N1 QKZUTMIQZDIZMR-UHFFFAOYSA-N 0.000 description 4
• CDPPVNICOXFMJN-UHFFFAOYSA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 CDPPVNICOXFMJN-UHFFFAOYSA-N 0.000 description 4
• JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 4
• SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 4
• 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 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 102100027587 Copper-transporting ATPase 1 Human genes 0.000 description 4
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
• 101000936277 Homo sapiens Copper-transporting ATPase 1 Proteins 0.000 description 4
• 206010024612 Lipoma Diseases 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 229960004050 aminobenzoic acid Drugs 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 230000003750 conditioning effect Effects 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 230000007123 defense Effects 0.000 description 4
• 230000009229 glucose formation Effects 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 239000001257 hydrogen Substances 0.000 description 4
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
• 208000030159 metabolic disease Diseases 0.000 description 4
• 125000002912 morpholin-4-ylsulfonyl group Chemical group O1C([H])([H])C([H])([H])N(S(=O)(=O)[*])C([H])([H])C1([H])[H] 0.000 description 4
• YJRGRZJKGMBHIB-UHFFFAOYSA-N n,n-dimethyl-3-piperazin-1-ylpropan-1-amine Chemical compound CN(C)CCCN1CCNCC1 YJRGRZJKGMBHIB-UHFFFAOYSA-N 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 3
• JTPXVCKCLBROOJ-UHFFFAOYSA-N 2-amino-6-chloropyrazine Chemical compound NC1=CN=CC(Cl)=N1 JTPXVCKCLBROOJ-UHFFFAOYSA-N 0.000 description 3
• FWQPUECKIFWEIL-UHFFFAOYSA-N 3-(1-benzofuran-2-yl)-5-bromopyrazin-2-amine Chemical compound NC1=NC=C(Br)N=C1C1=CC2=CC=CC=C2O1 FWQPUECKIFWEIL-UHFFFAOYSA-N 0.000 description 3
• ZNQDZVZVPNGXRN-UHFFFAOYSA-N 3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 ZNQDZVZVPNGXRN-UHFFFAOYSA-N 0.000 description 3
• GCTAZZRFYJDLHL-UHFFFAOYSA-N 4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2NC3=CC=C(F)C=C3C=2)=N1 GCTAZZRFYJDLHL-UHFFFAOYSA-N 0.000 description 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• VJOWMORERYNYON-UHFFFAOYSA-N 5-ethenyl-2-methylpyridine Chemical compound CC1=CC=C(C=C)C=N1 VJOWMORERYNYON-UHFFFAOYSA-N 0.000 description 3
• MOEWDKKPSZZLLA-UHFFFAOYSA-N 6-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 MOEWDKKPSZZLLA-UHFFFAOYSA-N 0.000 description 3
• DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
• 201000008808 Fibrosarcoma Diseases 0.000 description 3
• 208000017604 Hodgkin disease Diseases 0.000 description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
• 206010022489 Insulin Resistance Diseases 0.000 description 3
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 206010043276 Teratoma Diseases 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 238000011861 anti-inflammatory therapy Methods 0.000 description 3
• 125000002393 azetidinyl group Chemical group 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 102000015694 estrogen receptors Human genes 0.000 description 3
• 108010038795 estrogen receptors Proteins 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 206010016629 fibroma Diseases 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 201000011066 hemangioma Diseases 0.000 description 3
• 150000002431 hydrogen Chemical class 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 230000004155 insulin signaling pathway Effects 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
• 201000011453 reproductive organ cancer Diseases 0.000 description 3
• 208000015608 reproductive system cancer Diseases 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 229940124530 sulfonamide Drugs 0.000 description 3
• 150000003456 sulfonamides Chemical class 0.000 description 3
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• AVAWMINJNRAQFS-ZCFIWIBFSA-N (3r)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@@H]1CCNC1 AVAWMINJNRAQFS-ZCFIWIBFSA-N 0.000 description 2
• GAXWPRUSCYXXLH-UHFFFAOYSA-N (4-bromo-3-fluorophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Br)C(F)=C1 GAXWPRUSCYXXLH-UHFFFAOYSA-N 0.000 description 2
• OCDINFGZBOYESV-UHFFFAOYSA-N (4-bromo-3-methylphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Br)C(C)=C1 OCDINFGZBOYESV-UHFFFAOYSA-N 0.000 description 2
• COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 2
• 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 description 2
• FVACKFHRBNHCAP-UHFFFAOYSA-N 1-(4-bromo-2-fluorophenyl)sulfonyl-4-methylpiperazine Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(Br)C=C1F FVACKFHRBNHCAP-UHFFFAOYSA-N 0.000 description 2
• PKRRNTJIHGOMRC-UHFFFAOYSA-N 1-benzofuran-2-ylboronic acid Chemical compound C1=CC=C2OC(B(O)O)=CC2=C1 PKRRNTJIHGOMRC-UHFFFAOYSA-N 0.000 description 2
• WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
• WOMHDFKOLCAJMB-UHFFFAOYSA-N 2-(5-bromopyridin-3-yl)-1h-indole;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.BrC1=CN=CC(C=2NC3=CC=CC=C3C=2)=C1 WOMHDFKOLCAJMB-UHFFFAOYSA-N 0.000 description 2
• RTDBZIQZAHCJTH-UHFFFAOYSA-N 2-(6-chloropyrazin-2-yl)-1h-indole Chemical compound ClC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 RTDBZIQZAHCJTH-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 2
• ZNJRONVKWRHYBF-UHFFFAOYSA-N 2-[2-[2-(1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-7-yl)ethenyl]-6-methylpyran-4-ylidene]propanedinitrile Chemical compound O1C(C)=CC(=C(C#N)C#N)C=C1C=CC1=CC(CCCN2CCC3)=C2C3=C1 ZNJRONVKWRHYBF-UHFFFAOYSA-N 0.000 description 2
• ODQCVPQMOPXQMP-UHFFFAOYSA-N 2-chloro-4-[(6-chloropyrazin-2-yl)amino]benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=CC=C1NC1=CN=CC(Cl)=N1 ODQCVPQMOPXQMP-UHFFFAOYSA-N 0.000 description 2
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
• SOSPMXMEOFGPIM-UHFFFAOYSA-N 3,5-dibromopyridine Chemical compound BrC1=CN=CC(Br)=C1 SOSPMXMEOFGPIM-UHFFFAOYSA-N 0.000 description 2
• MKFWLXXVRVWWQL-UHFFFAOYSA-N 3-[(6-chloropyrazin-2-yl)amino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1NC1=CN=CC(Cl)=N1 MKFWLXXVRVWWQL-UHFFFAOYSA-N 0.000 description 2
• JGTKQMHVDKNRDW-UHFFFAOYSA-N 3-[[6-(1-benzofuran-2-yl)pyrazin-2-yl]amino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1NC1=CN=CC(C=2OC3=CC=CC=C3C=2)=N1 JGTKQMHVDKNRDW-UHFFFAOYSA-N 0.000 description 2
• KQIGMPWTAHJUMN-VKHMYHEASA-N 3-aminopropane-1,2-diol Chemical compound NC[C@H](O)CO KQIGMPWTAHJUMN-VKHMYHEASA-N 0.000 description 2
• KLSLJMGWUPAQGZ-UHFFFAOYSA-N 3-bromo-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(Br)=C1 KLSLJMGWUPAQGZ-UHFFFAOYSA-N 0.000 description 2
• FDPXNUCRFISRDD-UHFFFAOYSA-N 3-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 FDPXNUCRFISRDD-UHFFFAOYSA-N 0.000 description 2
• WYMCSVNDUHTYBE-UHFFFAOYSA-N 3-chloro-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]benzoic acid Chemical compound ClC1=CC(C(=O)O)=CC=C1NC1=CN=CC(C=2NC3=CC=C(F)C=C3C=2)=N1 WYMCSVNDUHTYBE-UHFFFAOYSA-N 0.000 description 2
• UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-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
• HBZAVQLQDUNDQR-UHFFFAOYSA-N 4-[(6-chloropyrazin-2-yl)amino]-2-fluorobenzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC=C1NC1=CN=CC(Cl)=N1 HBZAVQLQDUNDQR-UHFFFAOYSA-N 0.000 description 2
• UJXODJQPKKIYDS-UHFFFAOYSA-N 4-[(6-chloropyrazin-2-yl)amino]-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1NC1=CN=CC(Cl)=N1 UJXODJQPKKIYDS-UHFFFAOYSA-N 0.000 description 2
• DVQVKMSINZBRDI-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]benzoic acid Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(O)=O)N=C1C1=CC=C(O)C=C1 DVQVKMSINZBRDI-UHFFFAOYSA-N 0.000 description 2
• XVPQMSPGGXRNKH-UHFFFAOYSA-N 4-[[6-[5-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]pyrazin-2-yl]amino]-3-methoxybenzoic acid Chemical class COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2N(C3=CC=C(F)C=C3C=2)C(=O)OC(C)(C)C)=N1 XVPQMSPGGXRNKH-UHFFFAOYSA-N 0.000 description 2
• RVEATKYEARPWRE-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxybenzoic acid Chemical compound COC1=CC(N)=C(Cl)C=C1C(O)=O RVEATKYEARPWRE-UHFFFAOYSA-N 0.000 description 2
• KXRLQFWNLOWVBI-UHFFFAOYSA-N 4-bromo-2-methyl-n-(2-pyrrolidin-1-ylethyl)benzenesulfonamide Chemical compound CC1=CC(Br)=CC=C1S(=O)(=O)NCCN1CCCC1 KXRLQFWNLOWVBI-UHFFFAOYSA-N 0.000 description 2
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 2
• ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
• KRRTXVSBTPCDOS-UHFFFAOYSA-N 5-bromopyrazin-2-amine Chemical compound NC1=CN=C(Br)C=N1 KRRTXVSBTPCDOS-UHFFFAOYSA-N 0.000 description 2
• MDQXGHBCDCOOSM-UHFFFAOYSA-N 5-bromopyridin-3-amine Chemical compound NC1=CN=CC(Br)=C1 MDQXGHBCDCOOSM-UHFFFAOYSA-N 0.000 description 2
• JXDBWHOPYFKHEB-UHFFFAOYSA-N 5-chloro-4-[(6-chloropyrazin-2-yl)amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C(Cl)C=NC=2)=C1Cl JXDBWHOPYFKHEB-UHFFFAOYSA-N 0.000 description 2
• FMEBIWNKYZUWFV-UHFFFAOYSA-N 6-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)N=C1 FMEBIWNKYZUWFV-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 201000003076 Angiosarcoma 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
• 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• 208000001258 Hemangiosarcoma Diseases 0.000 description 2
• 102000006479 Heterogeneous-Nuclear Ribonucleoproteins Human genes 0.000 description 2
• 108010019372 Heterogeneous-Nuclear Ribonucleoproteins 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
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 description 2
• 201000004404 Neurofibroma Diseases 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 208000000035 Osteochondroma Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010034960 Photophobia Diseases 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000008383 Wilms tumor Diseases 0.000 description 2
• SROQNRJQESIGKW-UHFFFAOYSA-N [4-(5-amino-6-bromopyrazin-2-yl)phenyl]-morpholin-4-ylmethanone Chemical compound N1=C(Br)C(N)=NC=C1C1=CC=C(C(=O)N2CCOCC2)C=C1 SROQNRJQESIGKW-UHFFFAOYSA-N 0.000 description 2
• QRESLAZIBNCOJG-UHFFFAOYSA-N [4-(5-aminopyrazin-2-yl)phenyl]-morpholin-4-ylmethanone Chemical compound C1=NC(N)=CN=C1C1=CC=C(C(=O)N2CCOCC2)C=C1 QRESLAZIBNCOJG-UHFFFAOYSA-N 0.000 description 2
• LWEJVVPEHCUFRN-UHFFFAOYSA-N [4-[(6-chloropyrazin-2-yl)amino]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(Cl)=N1 LWEJVVPEHCUFRN-UHFFFAOYSA-N 0.000 description 2
• AHBMFEBTZKYPED-UHFFFAOYSA-N [5-chloro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound ClC1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 AHBMFEBTZKYPED-UHFFFAOYSA-N 0.000 description 2
• PZLVPMBCKHDVKT-UHFFFAOYSA-N [5-methoxy-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound COC1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 PZLVPMBCKHDVKT-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 125000005129 aryl carbonyl group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 230000006583 body weight regulation Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 208000002458 carcinoid tumor Diseases 0.000 description 2
• 230000024245 cell differentiation Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 229940126214 compound 3 Drugs 0.000 description 2
• 230000001143 conditioned effect Effects 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 2
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 230000004190 glucose uptake Effects 0.000 description 2
• 229960004275 glycolic acid Drugs 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 230000002440 hepatic effect Effects 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 201000010260 leiomyoma Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 206010027191 meningioma Diseases 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 208000025113 myeloid leukemia Diseases 0.000 description 2
• LGDNSGSJKBIVFG-UHFFFAOYSA-N n,n-dimethyl-2-piperazin-1-ylethanamine Chemical compound CN(C)CCN1CCNCC1 LGDNSGSJKBIVFG-UHFFFAOYSA-N 0.000 description 2
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
• 229940053128 nerve growth factor Drugs 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 159000000000 sodium salts Chemical class 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• ZGTQMRAFLPKCEO-UHFFFAOYSA-N tert-butyl 2-(5-aminopyridin-3-yl)indole-1-carboxylate Chemical compound C=1C2=CC=CC=C2N(C(=O)OC(C)(C)C)C=1C1=CN=CC(N)=C1 ZGTQMRAFLPKCEO-UHFFFAOYSA-N 0.000 description 2
• DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 2
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 230000035924 thermogenesis Effects 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 230000014616 translation Effects 0.000 description 2
• 230000008733 trauma Effects 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• NWYYWIJOWOLJNR-YFKPBYRVSA-N (2r)-2-amino-3-methylbutan-1-ol Chemical compound CC(C)[C@@H](N)CO NWYYWIJOWOLJNR-YFKPBYRVSA-N 0.000 description 1
• JOMNTHCQHJPVAZ-RXMQYKEDSA-N (2r)-2-methylpiperazine Chemical compound C[C@@H]1CNCCN1 JOMNTHCQHJPVAZ-RXMQYKEDSA-N 0.000 description 1
• JOMNTHCQHJPVAZ-YFKPBYRVSA-N (2s)-2-methylpiperazine Chemical compound C[C@H]1CNCCN1 JOMNTHCQHJPVAZ-YFKPBYRVSA-N 0.000 description 1
• IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 1
• FYVLZZSHUWYHAZ-UHFFFAOYSA-N (3-aminoazetidin-1-yl)-[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone;hydrochloride Chemical compound Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CC(N)C1 FYVLZZSHUWYHAZ-UHFFFAOYSA-N 0.000 description 1
• WDGWHKRJEBENCE-UHFFFAOYSA-N (3-carbamoylphenyl)boronic acid Chemical class NC(=O)C1=CC=CC(B(O)O)=C1 WDGWHKRJEBENCE-UHFFFAOYSA-N 0.000 description 1
• WFWQWTPAPNEOFE-UHFFFAOYSA-N (3-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(O)=C1 WFWQWTPAPNEOFE-UHFFFAOYSA-N 0.000 description 1
• 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 1
• AVAWMINJNRAQFS-LURJTMIESA-N (3s)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@H]1CCNC1 AVAWMINJNRAQFS-LURJTMIESA-N 0.000 description 1
• WTBSUAXLZLAHPE-UHFFFAOYSA-N (4-aminophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(N)C=C1 WTBSUAXLZLAHPE-UHFFFAOYSA-N 0.000 description 1
• WEHVQIQNGXWTME-UHFFFAOYSA-N (4-aminophenyl)-morpholin-4-ylmethanone Chemical class C1=CC(N)=CC=C1C(=O)N1CCOCC1 WEHVQIQNGXWTME-UHFFFAOYSA-N 0.000 description 1
• YILKCUJUEATIDR-UHFFFAOYSA-N (4-bromo-2-chlorophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Br)C=C1Cl YILKCUJUEATIDR-UHFFFAOYSA-N 0.000 description 1
• SSFVOHPVAZKIRO-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Br)C=C1F SSFVOHPVAZKIRO-UHFFFAOYSA-N 0.000 description 1
• NNRHWZYYIURZAO-UHFFFAOYSA-N (4-bromo-2-methylphenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(Br)C=C1C NNRHWZYYIURZAO-UHFFFAOYSA-N 0.000 description 1
• VLLKGCWVHHBZTR-UHFFFAOYSA-N (4-bromo-2-methylphenyl)-morpholin-4-ylmethanone Chemical compound CC1=CC(Br)=CC=C1C(=O)N1CCOCC1 VLLKGCWVHHBZTR-UHFFFAOYSA-N 0.000 description 1
• SGINYRFXUUMFLE-UHFFFAOYSA-N (4-bromo-3-methylphenyl)-morpholin-4-ylmethanone Chemical compound C1=C(Br)C(C)=CC(C(=O)N2CCOCC2)=C1 SGINYRFXUUMFLE-UHFFFAOYSA-N 0.000 description 1
• GNRHNKBJNUVWFZ-UHFFFAOYSA-N (4-carbamoylphenyl)boronic acid Chemical compound NC(=O)C1=CC=C(B(O)O)C=C1 GNRHNKBJNUVWFZ-UHFFFAOYSA-N 0.000 description 1
• NCJJBSPRMXVTIW-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone Chemical compound C1CN(CC)CCN1C(=O)C(C=C1OC)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 NCJJBSPRMXVTIW-UHFFFAOYSA-N 0.000 description 1
• JNQRUUBGEMDSNI-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[6-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]pyridin-3-yl]methanone Chemical compound C1CN(CC)CCN1C(=O)C(C=N1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 JNQRUUBGEMDSNI-UHFFFAOYSA-N 0.000 description 1
• SCCCDOPYCXBGPY-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-[[6-(1h-pyrrolo[2,3-c]pyridin-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CN=CC=C3C=2)=N1 SCCCDOPYCXBGPY-UHFFFAOYSA-N 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 1
• 125000000204 (C2-C4) acyl group Chemical group 0.000 description 1
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
• 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• FQWUIOJVBDSHQH-UHFFFAOYSA-N 1,2-diethylpyrazolidin-4-amine Chemical compound CCN1CC(N)CN1CC FQWUIOJVBDSHQH-UHFFFAOYSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• CWKVFRNCODQPDB-UHFFFAOYSA-N 1-(2-aminoethylamino)propan-2-ol Chemical compound CC(O)CNCCN CWKVFRNCODQPDB-UHFFFAOYSA-N 0.000 description 1
• BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
• YYKMFIBMFKKXJJ-UHFFFAOYSA-N 1-(4-bromo-2-methylphenyl)sulfonyl-4-methylpiperazine Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(Br)C=C1C YYKMFIBMFKKXJJ-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• YLBWRMSQRFEIEB-VIFPVBQESA-N 1-[[(2s)-pyrrolidin-2-yl]methyl]pyrrolidine Chemical compound C1CCCN1C[C@@H]1CCCN1 YLBWRMSQRFEIEB-VIFPVBQESA-N 0.000 description 1
• YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
• XPDSXKIDJNKIQY-UHFFFAOYSA-N 1-cyclohexylpiperazine Chemical compound C1CCCCC1N1CCNCC1 XPDSXKIDJNKIQY-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
• FSGHPNORMZCCST-UHFFFAOYSA-N 2-(5-bromopyridin-3-yl)-1h-indole Chemical compound BrC1=CN=CC(C=2NC3=CC=CC=C3C=2)=C1 FSGHPNORMZCCST-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• PJSDNCGHHIZQDQ-UHFFFAOYSA-N 2-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 PJSDNCGHHIZQDQ-UHFFFAOYSA-N 0.000 description 1
• 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• PXVBKAPYSTVXIP-UHFFFAOYSA-N 2-fluoro-4-[6-(4-hydroxyphenyl)pyrazin-2-yl]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide Chemical compound C1=CC(O)=CC=C1C1=CN=CC(C=2C=C(F)C(=CC=2)S(=O)(=O)NCCN2CCCC2)=N1 PXVBKAPYSTVXIP-UHFFFAOYSA-N 0.000 description 1
• JFGJBXVFOLMELM-UHFFFAOYSA-N 2-fluoro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 JFGJBXVFOLMELM-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• WFSJROCEOJANPD-UHFFFAOYSA-N 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound C1=C(O)C(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 WFSJROCEOJANPD-UHFFFAOYSA-N 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-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
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• 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 1
• JPXRVBGZPOECTQ-UHFFFAOYSA-N 3-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)=C1 JPXRVBGZPOECTQ-UHFFFAOYSA-N 0.000 description 1
• NDLPQJKEMDHEAF-UHFFFAOYSA-N 3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=CC=1C(=O)N(C)C1CCN(C)C1 NDLPQJKEMDHEAF-UHFFFAOYSA-N 0.000 description 1
• DMGFVJVLVZOSOE-UHFFFAOYSA-N 3-amino-4-chlorobenzoic acid Chemical compound NC1=CC(C(O)=O)=CC=C1Cl DMGFVJVLVZOSOE-UHFFFAOYSA-N 0.000 description 1
• FDGAEAYZQQCBRN-UHFFFAOYSA-N 3-amino-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1N FDGAEAYZQQCBRN-UHFFFAOYSA-N 0.000 description 1
• XKFIFYROMAAUDL-UHFFFAOYSA-N 3-amino-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N XKFIFYROMAAUDL-UHFFFAOYSA-N 0.000 description 1
• BFEUGUAUYFATRV-UHFFFAOYSA-N 3-bromopyrazin-2-amine Chemical compound NC1=NC=CN=C1Br BFEUGUAUYFATRV-UHFFFAOYSA-N 0.000 description 1
• ZHRBUSCAJPHBJY-UHFFFAOYSA-N 3-chloro-n-[2-(diethylamino)ethyl]-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]benzamide Chemical compound ClC1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2NC3=CC=C(F)C=C3C=2)=N1 ZHRBUSCAJPHBJY-UHFFFAOYSA-N 0.000 description 1
• OTOIUCLFSQHFOX-UHFFFAOYSA-N 3-sulfonylmorpholine Chemical compound O=S(=O)=C1COCCN1 OTOIUCLFSQHFOX-UHFFFAOYSA-N 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• QIKYZXDTTPVVAC-UHFFFAOYSA-N 4-Aminobenzamide Chemical compound NC(=O)C1=CC=C(N)C=C1 QIKYZXDTTPVVAC-UHFFFAOYSA-N 0.000 description 1
• RMYFSPMNSPBZHN-UHFFFAOYSA-N 4-[3-amino-6-(3-methyl-4-morpholin-4-ylsulfonylphenyl)pyrazin-2-yl]phenol Chemical compound CC1=CC(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)=CC=C1S(=O)(=O)N1CCOCC1 RMYFSPMNSPBZHN-UHFFFAOYSA-N 0.000 description 1
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
• HMPAZVKNAXLEFP-UHFFFAOYSA-N 4-[3-amino-6-[3-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrazin-2-yl]phenol Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)C=C1F HMPAZVKNAXLEFP-UHFFFAOYSA-N 0.000 description 1
• MXBAUVIEZCVWRR-UHFFFAOYSA-N 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]benzoic acid Chemical class N1=C(C=2OC3=CC=CC=C3C=2)C(N)=NC=C1C1=CC=C(C(O)=O)C=C1 MXBAUVIEZCVWRR-UHFFFAOYSA-N 0.000 description 1
• CNNOTYQZCYYEML-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-2-chloro-N-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound NC1=NC=C(C=2C=C(Cl)C(C(=O)NCCN3CCCC3)=CC=2)N=C1C1=CC=C(O)C=C1 CNNOTYQZCYYEML-UHFFFAOYSA-N 0.000 description 1
• LZHUMDROGFNNTA-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-2-fluoro-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide Chemical compound NC1=NC=C(C=2C=C(F)C(=CC=2)S(=O)(=O)NCCN2CCCC2)N=C1C1=CC=C(O)C=C1 LZHUMDROGFNNTA-UHFFFAOYSA-N 0.000 description 1
• DFLWHQQWPZAYNP-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide Chemical compound CC1=CC(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)=CC=C1S(=O)(=O)NCCN1CCCC1 DFLWHQQWPZAYNP-UHFFFAOYSA-N 0.000 description 1
• YEQPUXIGFPBFEO-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N,N-dimethylbenzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1=CN=C(N)C(C=2C=CC(O)=CC=2)=N1 YEQPUXIGFPBFEO-UHFFFAOYSA-N 0.000 description 1
• YICVIXFIOXUUMC-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-(2-morpholin-4-ylethyl)benzamide Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(=O)NCCN2CCOCC2)N=C1C1=CC=C(O)C=C1 YICVIXFIOXUUMC-UHFFFAOYSA-N 0.000 description 1
• HBRIPEOUUQZIAL-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-(furan-2-ylmethyl)benzamide Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(=O)NCC=2OC=CC=2)N=C1C1=CC=C(O)C=C1 HBRIPEOUUQZIAL-UHFFFAOYSA-N 0.000 description 1
• VAHVJWUMKZMNTD-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-benzyl-N-[2-(dimethylamino)ethyl]benzamide Chemical compound C=1C=C(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)C=CC=1C(=O)N(CCN(C)C)CC1=CC=CC=C1 VAHVJWUMKZMNTD-UHFFFAOYSA-N 0.000 description 1
• CCTVKTBJBSZTCX-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-cyclopentylbenzamide Chemical compound NC1=NC=C(N=C1C1=CC=C(O)C=C1)C1=CC=C(C=C1)C(=O)NC1CCCC1 CCTVKTBJBSZTCX-UHFFFAOYSA-N 0.000 description 1
• GROHILLFDSCXKM-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-ethyl-N-(2-hydroxyethyl)benzamide Chemical compound C1=CC(C(=O)N(CCO)CC)=CC=C1C1=CN=C(N)C(C=2C=CC(O)=CC=2)=N1 GROHILLFDSCXKM-UHFFFAOYSA-N 0.000 description 1
• CRBOPQXNDCWHHR-UHFFFAOYSA-N 4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-N-propan-2-ylbenzamide Chemical compound C1=CC(C(=O)NC(C)C)=CC=C1C1=CN=C(N)C(C=2C=CC(O)=CC=2)=N1 CRBOPQXNDCWHHR-UHFFFAOYSA-N 0.000 description 1
• IQGYWUQYNLKHOG-UHFFFAOYSA-N 4-[6-(1h-indol-2-yl)pyrazin-2-yl]benzoic acid Chemical class C1=CC(C(=O)O)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 IQGYWUQYNLKHOG-UHFFFAOYSA-N 0.000 description 1
• QMPWYZKJFJHAJH-UHFFFAOYSA-N 4-[6-(4-hydroxyphenyl)pyrazin-2-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide Chemical compound CC1=CC(C=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=CC=C1S(=O)(=O)NCCN1CCCC1 QMPWYZKJFJHAJH-UHFFFAOYSA-N 0.000 description 1
• ORZYOPKDTMCATM-UHFFFAOYSA-N 4-[6-(4-hydroxyphenyl)pyrazin-2-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=CN=CC(C=2C=CC(O)=CC=2)=N1 ORZYOPKDTMCATM-UHFFFAOYSA-N 0.000 description 1
• GDZHRVNJZFEIKJ-UHFFFAOYSA-N 4-[6-(4-hydroxyphenyl)pyrazin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CN=CC(C=2C=CC(O)=CC=2)=N1 GDZHRVNJZFEIKJ-UHFFFAOYSA-N 0.000 description 1
• VXARLBQGSAKCBO-UHFFFAOYSA-N 4-[[6-(1-benzofuran-2-yl)pyrazin-2-yl]amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2OC3=CC=CC=C3C=2)=N1 VXARLBQGSAKCBO-UHFFFAOYSA-N 0.000 description 1
• FPDGXYDYBWPHAL-ZEECNFPPSA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-[(3r)-pyrrolidin-3-yl]benzamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N[C@@H]1CCNC1 FPDGXYDYBWPHAL-ZEECNFPPSA-N 0.000 description 1
• FPDGXYDYBWPHAL-RMRYJAPISA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-[(3s)-pyrrolidin-3-yl]benzamide;dihydrochloride Chemical compound Cl.Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N[C@H]1CCNC1 FPDGXYDYBWPHAL-RMRYJAPISA-N 0.000 description 1
• VUPBHSWEMCUZES-UHFFFAOYSA-N 4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxy-n-piperidin-3-ylbenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)NC1CCCNC1 VUPBHSWEMCUZES-UHFFFAOYSA-N 0.000 description 1
• PELMQJAQQKKJHC-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C=1C=C(C(=O)NCCN2CCCC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 PELMQJAQQKKJHC-UHFFFAOYSA-N 0.000 description 1
• DXXZHRQZHRWJNR-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-(pyridin-2-ylmethyl)benzamide Chemical compound C=1C=C(C(=O)NCC=2N=CC=CC=2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 DXXZHRQZHRWJNR-UHFFFAOYSA-N 0.000 description 1
• WQHVSWHUNAZQQY-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C=1C=C(C(=O)N(C)C2CN(C)CC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 WQHVSWHUNAZQQY-UHFFFAOYSA-N 0.000 description 1
• BZFZLGFOUPEDNY-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxy-N-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound COC1=CC(C(=O)NCCN2CCCC2)=CC=C1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 BZFZLGFOUPEDNY-UHFFFAOYSA-N 0.000 description 1
• JFLAGDUSELRBLW-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxy-N-(pyridin-2-ylmethyl)benzamide Chemical compound COC1=CC(C(=O)NCC=2N=CC=CC=2)=CC=C1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 JFLAGDUSELRBLW-UHFFFAOYSA-N 0.000 description 1
• UWVFYBRWMYJAAV-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide Chemical compound COC1=CC(C(=O)N(C)C2CN(C)CC2)=CC=C1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 UWVFYBRWMYJAAV-UHFFFAOYSA-N 0.000 description 1
• PFGKWRHZCSLHFW-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C1=CC(O)=CC=C1C1=CN=CC(NC=2C=CC(=CC=2)C(=O)NCCN2CCCC2)=N1 PFGKWRHZCSLHFW-UHFFFAOYSA-N 0.000 description 1
• JJZIWWMWKHACIX-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-N-(pyridin-2-ylmethyl)benzamide Chemical compound C1=CC(O)=CC=C1C1=CN=CC(NC=2C=CC(=CC=2)C(=O)NCC=2N=CC=CC=2)=N1 JJZIWWMWKHACIX-UHFFFAOYSA-N 0.000 description 1
• LELZQDLHWARFFC-UHFFFAOYSA-N 4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 LELZQDLHWARFFC-UHFFFAOYSA-N 0.000 description 1
• AVFZYXUNQOHJDJ-UHFFFAOYSA-N 4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1NC1=CN=CC(C=2NC3=CC=C(F)C=C3C=2)=N1 AVFZYXUNQOHJDJ-UHFFFAOYSA-N 0.000 description 1
• MBDUKNCPOPMRJQ-UHFFFAOYSA-N 4-amino-2-chlorobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C(Cl)=C1 MBDUKNCPOPMRJQ-UHFFFAOYSA-N 0.000 description 1
• QHERSCUZBKDVOC-UHFFFAOYSA-N 4-amino-2-fluorobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C(F)=C1 QHERSCUZBKDVOC-UHFFFAOYSA-N 0.000 description 1
• OLJXRTRRJSMURJ-UHFFFAOYSA-N 4-amino-2-methoxybenzoic acid Chemical compound COC1=CC(N)=CC=C1C(O)=O OLJXRTRRJSMURJ-UHFFFAOYSA-N 0.000 description 1
• NHFKECPTBZZFBC-UHFFFAOYSA-N 4-amino-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1N NHFKECPTBZZFBC-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• RMYOGXPGIDWJLU-UHFFFAOYSA-N 4-bromo-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(F)=C1 RMYOGXPGIDWJLU-UHFFFAOYSA-N 0.000 description 1
• DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
• VILDYEPNCMAYFV-UHFFFAOYSA-N 4-chloro-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide Chemical compound C1=C(NC2=C(C=CC(C(=O)N(C3CN(CC3)C)C)=C2)Cl)N=C(C2=CC=C(O)C=C2)C=N1 VILDYEPNCMAYFV-UHFFFAOYSA-N 0.000 description 1
• UJRCTEBWTLIGHT-UHFFFAOYSA-N 4-chloro-N-[2-(diethylamino)ethyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzamide Chemical compound C=1(C=NC=C(N=1)NC1=CC(C(=O)NCCN(CC)CC)=CC=C1Cl)C1=CC=C(O)C=C1 UJRCTEBWTLIGHT-UHFFFAOYSA-N 0.000 description 1
• MEVBCIQURCHFSF-UHFFFAOYSA-N 4-chloro-N-[2-(dimethylamino)ethyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzamide Chemical compound C1(NC2=CC(=CC=C2Cl)C(=O)NCCN(C)C)=NC(C2=CC=C(O)C=C2)=CN=C1 MEVBCIQURCHFSF-UHFFFAOYSA-N 0.000 description 1
• WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
• 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 1
• BJLVAOQVXIDOLA-UHFFFAOYSA-N 5-bromo-3-(1h-indol-2-yl)pyrazin-2-amine Chemical compound NC1=NC=C(Br)N=C1C1=CC2=CC=CC=C2N1 BJLVAOQVXIDOLA-UHFFFAOYSA-N 0.000 description 1
• CLXWJROWKWBAHU-UHFFFAOYSA-N 5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-(2-morpholin-4-ylethyl)benzamide Chemical compound ClC=1C=C(C(=O)NCCN2CCOCC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 CLXWJROWKWBAHU-UHFFFAOYSA-N 0.000 description 1
• RJGYBHRLASJSIM-UHFFFAOYSA-N 5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-(oxolan-2-ylmethyl)benzamide Chemical compound ClC=1C=C(C(=O)NCC2OCCC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 RJGYBHRLASJSIM-UHFFFAOYSA-N 0.000 description 1
• QJYINVURFKSHMN-UHFFFAOYSA-N 5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide Chemical compound ClC=1C=C(C(=O)N(C)C2CN(C)CC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 QJYINVURFKSHMN-UHFFFAOYSA-N 0.000 description 1
• VGPIJRJAQIMJOF-UHFFFAOYSA-N 5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-N-[2-(2-hydroxypropylamino)ethyl]-2-methoxybenzamide Chemical compound C1=C(C(=O)NCCNCC(C)O)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl VGPIJRJAQIMJOF-UHFFFAOYSA-N 0.000 description 1
• VEKKEQAPFRKQGH-UHFFFAOYSA-N 5-chloro-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)=C1Cl VEKKEQAPFRKQGH-UHFFFAOYSA-N 0.000 description 1
• FBSWUKFQYTYCCA-UHFFFAOYSA-N 5-chloro-N-[2-(diethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound C1=C(OC)C(C(=O)NCCN(CC)CC)=CC(Cl)=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 FBSWUKFQYTYCCA-UHFFFAOYSA-N 0.000 description 1
• AABWGYDGBGCDJM-UHFFFAOYSA-N 5-chloro-N-[2-(dimethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-methylbenzamide Chemical compound C1=C(C(=O)N(C)CCN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl AABWGYDGBGCDJM-UHFFFAOYSA-N 0.000 description 1
• OTZHESKVEMUCKU-UHFFFAOYSA-N 5-chloro-N-[2-(dimethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound C1=C(C(=O)NCCN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl OTZHESKVEMUCKU-UHFFFAOYSA-N 0.000 description 1
• ZAUASZYWLJJGTB-UHFFFAOYSA-N 5-chloro-N-[3-(dimethylamino)-2,2-dimethylpropyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound C1=C(C(=O)NCC(C)(C)CN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl ZAUASZYWLJJGTB-UHFFFAOYSA-N 0.000 description 1
• CWPQHWFQUIUMPW-UHFFFAOYSA-N 5-chloro-N-[3-(dimethylamino)propyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxy-N-methylbenzamide Chemical compound C1=C(C(=O)N(C)CCCN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl CWPQHWFQUIUMPW-UHFFFAOYSA-N 0.000 description 1
• MPUUMNQOURZIEO-UHFFFAOYSA-N 5-chloro-N-[3-(dimethylamino)propyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound C1=C(C(=O)NCCCN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1Cl MPUUMNQOURZIEO-UHFFFAOYSA-N 0.000 description 1
• OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 206010006811 Bursitis Diseases 0.000 description 1
• SSUFDOMYCBCHML-UHFFFAOYSA-N CCCCC[S](=O)=O Chemical group CCCCC[S](=O)=O SSUFDOMYCBCHML-UHFFFAOYSA-N 0.000 description 1
• MEFIGEXUHFWIIC-UHFFFAOYSA-N CN1CCN(CC1)C(=O)C1=CC=C(C=C1)B1OC(C(C1)(C)C)(C)C Chemical compound CN1CCN(CC1)C(=O)C1=CC=C(C=C1)B1OC(C(C1)(C)C)(C)C MEFIGEXUHFWIIC-UHFFFAOYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 241000222122 Candida albicans Species 0.000 description 1
• 206010007134 Candida infections Diseases 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 208000009458 Carcinoma in Situ Diseases 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 208000006332 Choriocarcinoma Diseases 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 102000003910 Cyclin D Human genes 0.000 description 1
• 108090000259 Cyclin D Proteins 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
• 208000007033 Dysgerminoma Diseases 0.000 description 1
• 206010013935 Dysmenorrhoea Diseases 0.000 description 1
• 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 108060002636 Eukaryotic Initiation Factor-4E Proteins 0.000 description 1
• 102000005233 Eukaryotic Initiation Factor-4E Human genes 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
• 206010016717 Fistula Diseases 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 206010017943 Gastrointestinal conditions Diseases 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 208000000527 Germinoma Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 201000005409 Gliomatosis cerebri Diseases 0.000 description 1
• 206010018404 Glucagonoma Diseases 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 206010018634 Gouty Arthritis Diseases 0.000 description 1
• 206010018691 Granuloma Diseases 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000002927 Hamartoma Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 206010019629 Hepatic adenoma Diseases 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000573522 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 description 1
• 101001018978 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 description 1
• 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
• 101000702384 Homo sapiens Protein sprouty homolog 2 Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 208000000913 Kidney Calculi Diseases 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
• 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 201000004458 Myoma Diseases 0.000 description 1
• APXPZFAPFXUKBI-UHFFFAOYSA-N N-(1-benzylpiperidin-4-yl)-5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound ClC=1C=C(C(=O)NC2CCN(CC=3C=CC=CC=3)CC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 APXPZFAPFXUKBI-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• VRTYGEUXUOZTMG-UHFFFAOYSA-N N-[2-(diethylamino)ethyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methoxybenzamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.C(C)N(CCNC(C1=CC(=C(C=C1)OC)NC1=NC(=CN=C1)C1=CC=C(C=C1)O)=O)CC VRTYGEUXUOZTMG-UHFFFAOYSA-N 0.000 description 1
• WWDJZFAPUBRECO-UHFFFAOYSA-N N-[2-(diethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound CCN(CC)CCNC(=O)C1=C(OC)C=C(NC2=CN=CC(=N2)C2=CC=C(O)C=C2)C=C1 WWDJZFAPUBRECO-UHFFFAOYSA-N 0.000 description 1
• HGCGKZUGWGRMNT-UHFFFAOYSA-N N-[2-(diethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 HGCGKZUGWGRMNT-UHFFFAOYSA-N 0.000 description 1
• OFFFFSNRKUUXHD-UHFFFAOYSA-N N-[2-(diethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzamide Chemical compound C1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 OFFFFSNRKUUXHD-UHFFFAOYSA-N 0.000 description 1
• OKEPFVQFTBMUNS-UHFFFAOYSA-N N-[2-(dimethylamino)ethyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methoxybenzamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CN(CCNC(C1=CC(=C(C=C1)OC)NC1=NC(=CN=C1)C1=CC=C(C=C1)O)=O)C OKEPFVQFTBMUNS-UHFFFAOYSA-N 0.000 description 1
• PCYXPXVEPZAFMF-UHFFFAOYSA-N N-[2-(dimethylamino)ethyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 PCYXPXVEPZAFMF-UHFFFAOYSA-N 0.000 description 1
• FUHCUOGEEFEKBD-UHFFFAOYSA-N N-[2-(dimethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCN(C)C)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 FUHCUOGEEFEKBD-UHFFFAOYSA-N 0.000 description 1
• PBZFXNUVQQYMIF-UHFFFAOYSA-N N-[2-(dimethylamino)ethyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]benzamide Chemical compound C1=CC(C(=O)NCCN(C)C)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 PBZFXNUVQQYMIF-UHFFFAOYSA-N 0.000 description 1
• PCFSPEBLNWVSTO-UHFFFAOYSA-N N-[3-(dimethylamino)propyl]-3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methoxybenzamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CN(CCCNC(C1=CC(=C(C=C1)OC)NC1=NC(=CN=C1)C1=CC=C(C=C1)O)=O)C PCFSPEBLNWVSTO-UHFFFAOYSA-N 0.000 description 1
• LPJYGEDLRLHEIL-UHFFFAOYSA-N N-[3-(dimethylamino)propyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxybenzamide Chemical compound C1=C(C(=O)NCCCN(C)C)C(OC)=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 LPJYGEDLRLHEIL-UHFFFAOYSA-N 0.000 description 1
• SRDKQDFZWMMWKH-UHFFFAOYSA-N N-[3-(dimethylamino)propyl]-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCCN(C)C)=CC=C1NC1=CN=CC(C=2C=CC(O)=CC=2)=N1 SRDKQDFZWMMWKH-UHFFFAOYSA-N 0.000 description 1
• 229910004809 Na2 SO4 Inorganic materials 0.000 description 1
• 206010029148 Nephrolithiasis Diseases 0.000 description 1
• 206010029164 Nephrotic syndrome Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• UHJFMAJYDZKDLJ-UHFFFAOYSA-N OBO.OC1=CC=CC=C1 Chemical compound OBO.OC1=CC=CC=C1 UHJFMAJYDZKDLJ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 102000043276 Oncogene Human genes 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010031149 Osteitis Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 208000007641 Pinealoma Diseases 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 108010076181 Proinsulin Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 206010037423 Pulmonary oedema Diseases 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 101100473045 Rattus norvegicus Hnrnpa2b1 gene Proteins 0.000 description 1
• 206010038910 Retinitis Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 208000005678 Rhabdomyoma Diseases 0.000 description 1
• 208000025747 Rheumatic disease Diseases 0.000 description 1
• 229910006124 SOCl2 Inorganic materials 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
• 208000006045 Spondylarthropathies Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 208000007107 Stomach Ulcer Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 206010042674 Swelling Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000000491 Tendinopathy Diseases 0.000 description 1
• 206010043255 Tendonitis Diseases 0.000 description 1
• 206010043269 Tension headache Diseases 0.000 description 1
• 208000008548 Tension-Type Headache Diseases 0.000 description 1
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 208000009311 VIPoma Diseases 0.000 description 1
• 206010046914 Vaginal infection Diseases 0.000 description 1
• 201000008100 Vaginitis Diseases 0.000 description 1
• 206010046996 Varicose vein Diseases 0.000 description 1
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 206010048214 Xanthoma Diseases 0.000 description 1
• 206010048215 Xanthomatosis Diseases 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• VDYDRLVLIYNHGC-VEIFNGETSA-N [(3r)-3-(dimethylamino)pyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1[C@H](N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 VDYDRLVLIYNHGC-VEIFNGETSA-N 0.000 description 1
• CRAKYNBTEKLLLC-ZEECNFPPSA-N [(3r)-3-aminopyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CC[C@@H](N)C1 CRAKYNBTEKLLLC-ZEECNFPPSA-N 0.000 description 1
• SIQTVFFZQISFDN-ZEECNFPPSA-N [(3r)-3-aminopyrrolidin-1-yl]-[4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CC[C@@H](N)C1 SIQTVFFZQISFDN-ZEECNFPPSA-N 0.000 description 1
• IYIMGJPMKSLGNJ-IBGZPJMESA-N [(3s)-3-(dimethylamino)pyrrolidin-1-yl]-[3-methoxy-4-[[6-(5-nitro-1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(C=C3C=2)[N+]([O-])=O)C(OC)=CC=1C(=O)N1CC[C@H](N(C)C)C1 IYIMGJPMKSLGNJ-IBGZPJMESA-N 0.000 description 1
• CRAKYNBTEKLLLC-RMRYJAPISA-N [(3s)-3-aminopyrrolidin-1-yl]-[4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CC[C@H](N)C1 CRAKYNBTEKLLLC-RMRYJAPISA-N 0.000 description 1
• YXJBIADEQVCONT-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenylmethoxyindol-2-yl]boronic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1OCC1=CC=CC=C1 YXJBIADEQVCONT-UHFFFAOYSA-N 0.000 description 1
• XALVHLSGJNNUFQ-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]-5-nitroindol-2-yl]boronic acid Chemical compound [O-][N+](=O)C1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 XALVHLSGJNNUFQ-UHFFFAOYSA-N 0.000 description 1
• HMDKFLVMSBTJGK-UHFFFAOYSA-N [2-chloro-4-[6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C1=CC(O)=CC=C1C1=CN=CC(C=2C=C(Cl)C(C(=O)N3CCOCC3)=CC=2)=N1 HMDKFLVMSBTJGK-UHFFFAOYSA-N 0.000 description 1
• RHBNYPZVWUBPOV-UHFFFAOYSA-N [2-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.ClC1=CC(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)=CC=C1C(=O)N1CCNCC1 RHBNYPZVWUBPOV-UHFFFAOYSA-N 0.000 description 1
• HDYLFCCIGKPJCU-UHFFFAOYSA-N [2-hydroxy-5-[6-[4-(morpholine-4-carbonyl)phenyl]pyrazin-2-yl]phenyl]-phenylmethanone Chemical compound OC1=CC=C(C=2N=C(C=NC=2)C=2C=CC(=CC=2)C(=O)N2CCOCC2)C=C1C(=O)C1=CC=CC=C1 HDYLFCCIGKPJCU-UHFFFAOYSA-N 0.000 description 1
• BYRIHRGFMYXTLC-UHFFFAOYSA-N [3-(furan-2-ylmethylcarbamoyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(=O)NCC=2OC=CC=2)=C1 BYRIHRGFMYXTLC-UHFFFAOYSA-N 0.000 description 1
• DRZFURCXDFRZNR-UHFFFAOYSA-N [3-(morpholine-4-carbonyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(=O)N2CCOCC2)=C1 DRZFURCXDFRZNR-UHFFFAOYSA-N 0.000 description 1
• RSYYSGOXHAKQSI-UHFFFAOYSA-N [3-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound NC1=NC=C(C=2C=C(C=CC=2)C(=O)N2CCOCC2)N=C1C1=CC=C(O)C=C1 RSYYSGOXHAKQSI-UHFFFAOYSA-N 0.000 description 1
• KDKUZGRGPWBDQD-UHFFFAOYSA-N [3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.COC1=C(C=C(C=C1)C(=O)N1CCN(CC1)C)NC1=CN=CC(=N1)C1=CC=C(C=C1)O KDKUZGRGPWBDQD-UHFFFAOYSA-N 0.000 description 1
• OAAVXQLLLZEEGN-UHFFFAOYSA-N [3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-4-methylphenyl]-(4-methylpiperazin-1-yl)methanone 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CC1=C(C=C(C=C1)C(=O)N1CCN(CC1)C)NC1=CN=CC(=N1)C1=CC=C(C=C1)O OAAVXQLLLZEEGN-UHFFFAOYSA-N 0.000 description 1
• QJTGTGHDFXBIMG-UHFFFAOYSA-N [3-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=CC(NC=2N=C(C=NC=2)C=2C=CC(O)=CC=2)=C1 QJTGTGHDFXBIMG-UHFFFAOYSA-N 0.000 description 1
• ZZUOQKXUVLNPHV-UHFFFAOYSA-N [3-chloro-4-(morpholin-4-ylcarbamoyl)phenyl]boronic acid Chemical compound ClC1=CC(B(O)O)=CC=C1C(=O)NN1CCOCC1 ZZUOQKXUVLNPHV-UHFFFAOYSA-N 0.000 description 1
• BNENSLWVUCRECV-UHFFFAOYSA-N [3-chloro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(Cl)=CC=1C(=O)N1CCNCC1 BNENSLWVUCRECV-UHFFFAOYSA-N 0.000 description 1
• KLLJDODWDCIHTN-UHFFFAOYSA-N [3-chloro-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]phenyl]-piperazin-1-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(F)=CC=C2NC=1C(N=1)=CN=CC=1NC(C(=C1)Cl)=CC=C1C(=O)N1CCNCC1 KLLJDODWDCIHTN-UHFFFAOYSA-N 0.000 description 1
• OYWGCGGTQRVVRG-UHFFFAOYSA-N [3-fluoro-4-[6-(1h-indol-2-yl)pyrazin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(F)=C1 OYWGCGGTQRVVRG-UHFFFAOYSA-N 0.000 description 1
• APJISWFEQVISDA-UHFFFAOYSA-N [3-fluoro-4-[6-(1h-indol-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(F)=CC=1C(=O)N1CCOCC1 APJISWFEQVISDA-UHFFFAOYSA-N 0.000 description 1
• LMWOYSUSPPTGGC-UHFFFAOYSA-N [4-(6-chloropyrazin-2-yl)phenyl]-morpholin-4-ylmethanone Chemical compound ClC1=CN=CC(C=2C=CC(=CC=2)C(=O)N2CCOCC2)=N1 LMWOYSUSPPTGGC-UHFFFAOYSA-N 0.000 description 1
• KMNLIQJXZPBCDU-UHFFFAOYSA-N [4-(morpholine-4-carbonyl)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1C(=O)N1CCOCC1 KMNLIQJXZPBCDU-UHFFFAOYSA-N 0.000 description 1
• MAYKYBGWFAAOBS-CYBMUJFWSA-N [4-[(6-chloropyrazin-2-yl)amino]-3-methoxyphenyl]-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical compound COC1=CC(C(=O)N2C[C@@H](CC2)N(C)C)=CC=C1NC1=CN=CC(Cl)=N1 MAYKYBGWFAAOBS-CYBMUJFWSA-N 0.000 description 1
• MAYKYBGWFAAOBS-ZDUSSCGKSA-N [4-[(6-chloropyrazin-2-yl)amino]-3-methoxyphenyl]-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical class COC1=CC(C(=O)N2C[C@H](CC2)N(C)C)=CC=C1NC1=CN=CC(Cl)=N1 MAYKYBGWFAAOBS-ZDUSSCGKSA-N 0.000 description 1
• AMXQSVXXPXIFMM-UHFFFAOYSA-N [4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound N1=C(C=2OC3=CC=CC=C3C=2)C(N)=NC=C1C(C=C1)=CC=C1C(=O)N1CCOCC1 AMXQSVXXPXIFMM-UHFFFAOYSA-N 0.000 description 1
• FTZXELIUUGJIFS-UHFFFAOYSA-N [4-[5-amino-6-(1h-indol-2-yl)pyrazin-2-yl]-3-fluorophenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2NC3=CC=CC=C3C=2)C(F)=C1 FTZXELIUUGJIFS-UHFFFAOYSA-N 0.000 description 1
• VPFRZHOQKVNULN-UHFFFAOYSA-N [4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-2-fluorophenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)C=C1F VPFRZHOQKVNULN-UHFFFAOYSA-N 0.000 description 1
• OXQADRQBVLYVBC-UHFFFAOYSA-N [4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]-2-methylphenyl]-(4-methylpiperazin-1-yl)methanone 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.NC=1C(=NC(=CN1)C1=CC(=C(C=C1)C(=O)N1CCN(CC1)C)C)C1=CC=C(C=C1)O OXQADRQBVLYVBC-UHFFFAOYSA-N 0.000 description 1
• OVMGAAQSOAYNOE-UHFFFAOYSA-N [4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N=C(C(N)=NC=2)C=2C=CC(O)=CC=2)C=C1 OVMGAAQSOAYNOE-UHFFFAOYSA-N 0.000 description 1
• BQLMOCXGDXVLQM-UHFFFAOYSA-N [4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-[4-(hydroxymethyl)piperidin-1-yl]methanone Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(=O)N2CCC(CO)CC2)N=C1C1=CC=C(O)C=C1 BQLMOCXGDXVLQM-UHFFFAOYSA-N 0.000 description 1
• LIRYWPVMIJIWGN-UHFFFAOYSA-N [4-[5-amino-6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(=O)N2CCOCC2)N=C1C1=CC=C(O)C=C1 LIRYWPVMIJIWGN-UHFFFAOYSA-N 0.000 description 1
• YZGNEDJYWQSVHT-UHFFFAOYSA-N [4-[6-(1-benzothiophen-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C=2N=C(C=NC=2)C=2SC3=CC=CC=C3C=2)C=CC=1C(=O)N1CCOCC1 YZGNEDJYWQSVHT-UHFFFAOYSA-N 0.000 description 1
• CUSBASMLBLPZHG-UHFFFAOYSA-N [4-[6-(1h-indol-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C(C=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C=CC=1C(=O)N1CCOCC1 CUSBASMLBLPZHG-UHFFFAOYSA-N 0.000 description 1
• OZUGTEDCNXKNTR-UHFFFAOYSA-N [4-[6-(1h-indol-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone;hydrochloride Chemical compound Cl.C=1C=C(C=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C=CC=1C(=O)N1CCOCC1 OZUGTEDCNXKNTR-UHFFFAOYSA-N 0.000 description 1
• PGWDCXHKMBMAIX-UHFFFAOYSA-N [4-[6-(4-hydroxyphenyl)pyrazin-2-yl]-3-methylphenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N=C(C=NC=2)C=2C=CC(O)=CC=2)C(C)=C1 PGWDCXHKMBMAIX-UHFFFAOYSA-N 0.000 description 1
• MNQANIBZRNNLKR-UHFFFAOYSA-N [4-[6-(4-hydroxyphenyl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C1=CC(O)=CC=C1C1=CN=CC(C=2C=CC(=CC=2)C(=O)N2CCOCC2)=N1 MNQANIBZRNNLKR-UHFFFAOYSA-N 0.000 description 1
• DGUSNOWIXMESGU-UHFFFAOYSA-N [4-[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(N=1)=CN=CC=1C(C=C1)=CC=C1C(=O)N1CCOCC1 DGUSNOWIXMESGU-UHFFFAOYSA-N 0.000 description 1
• SGRLBYYCMNMZOL-UHFFFAOYSA-N [4-[[5-(1h-indol-2-yl)pyridin-3-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=C1 SGRLBYYCMNMZOL-UHFFFAOYSA-N 0.000 description 1
• VYTBTGLIMYZDAJ-UHFFFAOYSA-N [4-[[5-(5-fluoro-1h-indol-2-yl)pyridin-3-yl]amino]phenyl]-piperazin-1-ylmethanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(C=1)=CN=CC=1NC(C=C1)=CC=C1C(=O)N1CCNCC1 VYTBTGLIMYZDAJ-UHFFFAOYSA-N 0.000 description 1
• JHLYSHJWXMJURV-UHFFFAOYSA-N [4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCCN(C)CC1 JHLYSHJWXMJURV-UHFFFAOYSA-N 0.000 description 1
• FLPNFBIFODLXOT-UHFFFAOYSA-N [4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCN(C)CC1 FLPNFBIFODLXOT-UHFFFAOYSA-N 0.000 description 1
• KBBVSVHVBNJUIA-UHFFFAOYSA-N [4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-morpholin-4-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)C(OC)=CC=1C(=O)N1CCOCC1 KBBVSVHVBNJUIA-UHFFFAOYSA-N 0.000 description 1
• OSNHOIAPOGIUNY-UHFFFAOYSA-N [4-[[6-(4-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-piperazin-1-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC(F)=C3C=2)C(OC)=CC=1C(=O)N1CCNCC1 OSNHOIAPOGIUNY-UHFFFAOYSA-N 0.000 description 1
• TULDDCJHSUMABO-UHFFFAOYSA-N [4-[[6-(4-hydroxy-1H-indol-2-yl)pyrazin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.CN1CCN(CC1)C(=O)C1=CC=C(C=C1)NC1=CN=CC(=N1)C=1NC=2C=CC=C(C2C1)O TULDDCJHSUMABO-UHFFFAOYSA-N 0.000 description 1
• YGFKKQDHGSOQSE-UHFFFAOYSA-N [4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-3-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound COC1=CC(C(=O)N2CCN(C)CC2)=CC=C1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 YGFKKQDHGSOQSE-UHFFFAOYSA-N 0.000 description 1
• PTBDLNLDKYUZHG-UHFFFAOYSA-N [4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)N1CCN(C)CC1 PTBDLNLDKYUZHG-UHFFFAOYSA-N 0.000 description 1
• GIHZCAVQMVZATP-UHFFFAOYSA-N [4-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1F GIHZCAVQMVZATP-UHFFFAOYSA-N 0.000 description 1
• BEXQWPHMBFKSLF-UHFFFAOYSA-N [4-methoxy-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound COC1=CC=CC2=C1C=C(B(O)O)N2C(=O)OC(C)(C)C BEXQWPHMBFKSLF-UHFFFAOYSA-N 0.000 description 1
• BDAFYQPNCMBBGU-UHFFFAOYSA-N [5-[[5-(5-fluoro-1h-indol-2-yl)pyridin-3-yl]amino]pyridin-2-yl]-piperazin-1-ylmethanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(C=1)=CN=CC=1NC(C=N1)=CC=C1C(=O)N1CCNCC1 BDAFYQPNCMBBGU-UHFFFAOYSA-N 0.000 description 1
• BZEIEXSUBVPJGW-UHFFFAOYSA-N [5-[[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino]pyridin-2-yl]-piperazin-1-ylmethanone 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C=1C2=CC(F)=CC=C2NC=1C(N=1)=CN=CC=1NC(C=N1)=CC=C1C(=O)N1CCNCC1 BZEIEXSUBVPJGW-UHFFFAOYSA-N 0.000 description 1
• USSSKMVUCQDPLU-UHFFFAOYSA-N [5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxyphenyl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound ClC=1C=C(C(=O)N2CCN(C)CCC2)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 USSSKMVUCQDPLU-UHFFFAOYSA-N 0.000 description 1
• RVCRQYVEDIYVOI-UHFFFAOYSA-N [5-chloro-4-[[6-(4-hydroxyphenyl)pyrazin-2-yl]amino]-2-methoxyphenyl]-[2-[(dimethylamino)methyl]piperidin-1-yl]methanone Chemical compound ClC=1C=C(C(=O)N2C(CCCC2)CN(C)C)C(OC)=CC=1NC(N=1)=CN=CC=1C1=CC=C(O)C=C1 RVCRQYVEDIYVOI-UHFFFAOYSA-N 0.000 description 1
• SGZZDZSEIDVCFE-UHFFFAOYSA-N [5-chloro-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-2-methoxyphenyl]-piperazin-1-ylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)=C(Cl)C=C1C(=O)N1CCNCC1 SGZZDZSEIDVCFE-UHFFFAOYSA-N 0.000 description 1
• AJWYBPNMPKTRDV-UHFFFAOYSA-N [5-cyano-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound N#CC1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 AJWYBPNMPKTRDV-UHFFFAOYSA-N 0.000 description 1
• PEOOUPNYKOKTRH-UHFFFAOYSA-N [5-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound CC1=CC=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 PEOOUPNYKOKTRH-UHFFFAOYSA-N 0.000 description 1
• ZUBSLPYPWNMPQS-UHFFFAOYSA-N [6-[(6-chloropyrazin-2-yl)amino]pyridin-3-yl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound C1CN(C)CCCN1C(=O)C(C=N1)=CC=C1NC1=CN=CC(Cl)=N1 ZUBSLPYPWNMPQS-UHFFFAOYSA-N 0.000 description 1
• FLHZZIIHBLTSNH-UHFFFAOYSA-N [6-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]pyridin-3-yl]-morpholin-4-ylmethanone Chemical compound C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=CC=C3C=2)N=CC=1C(=O)N1CCOCC1 FLHZZIIHBLTSNH-UHFFFAOYSA-N 0.000 description 1
• AHUWHEZTYPWOCY-UHFFFAOYSA-N [6-chloro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=C(Cl)C=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 AHUWHEZTYPWOCY-UHFFFAOYSA-N 0.000 description 1
• GARRUKBUEWVRCV-UHFFFAOYSA-N [6-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=C(F)C=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 GARRUKBUEWVRCV-UHFFFAOYSA-N 0.000 description 1
• KLHBTAWDTXMJLT-UHFFFAOYSA-N [6-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound CC1=CC=C2C=C(B(O)O)N(C(=O)OC(C)(C)C)C2=C1 KLHBTAWDTXMJLT-UHFFFAOYSA-N 0.000 description 1
• AHFAZIPJGLAFSE-UHFFFAOYSA-N [7-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C1=CC(F)=C2N(C(=O)OC(C)(C)C)C(B(O)O)=CC2=C1 AHFAZIPJGLAFSE-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 235000011054 acetic acid Nutrition 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 208000002718 adenomatoid tumor Diseases 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 230000009435 amidation Effects 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000005415 aminobenzoic acids Chemical class 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 206010003246 arthritis Diseases 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
• 208000006673 asthma Diseases 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 208000001119 benign fibrous histiocytoma Diseases 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
• 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
• 150000001559 benzoic acids Chemical class 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 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
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 230000036983 biotransformation Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 208000018339 bone inflammation disease Diseases 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 201000003984 candidiasis Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000036978 cell physiology Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 230000001054 cortical effect Effects 0.000 description 1
• 201000010305 cutaneous fibrous histiocytoma Diseases 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 235000005686 eating Nutrition 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 230000019439 energy homeostasis Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 230000008713 feedback mechanism Effects 0.000 description 1
• 230000003890 fistula Effects 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• SADPINFEWFPMEA-UHFFFAOYSA-N furan-2-yl(piperazin-1-yl)methanone Chemical compound C=1C=COC=1C(=O)N1CCNCC1 SADPINFEWFPMEA-UHFFFAOYSA-N 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 201000005917 gastric ulcer Diseases 0.000 description 1
• 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
• 201000000052 gastrinoma Diseases 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 210000004392 genitalia Anatomy 0.000 description 1
• 201000003115 germ cell cancer Diseases 0.000 description 1
• 208000007565 gingivitis Diseases 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 230000014101 glucose homeostasis Effects 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 208000035474 group of disease Diseases 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229960001867 guaiacol Drugs 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000024348 heart neoplasm Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 208000006359 hepatoblastoma Diseases 0.000 description 1
• 201000002735 hepatocellular adenoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• 102000057747 human MKNK1 Human genes 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• 230000009610 hypersensitivity Effects 0.000 description 1
• AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 201000004933 in situ carcinoma Diseases 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003914 insulin secretion Effects 0.000 description 1
• 206010022498 insulinoma Diseases 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 210000002570 interstitial cell Anatomy 0.000 description 1
• 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 208000002551 irritable bowel syndrome Diseases 0.000 description 1
• 210000004153 islets of langerhan Anatomy 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
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 208000022013 kidney Wilms tumor Diseases 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960000448 lactic acid Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960001375 lactose Drugs 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 150000002605 large molecules Chemical class 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229940098895 maleic acid Drugs 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 201000004593 malignant giant cell tumor Diseases 0.000 description 1
• 201000000289 malignant teratoma Diseases 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 102000006240 membrane receptors Human genes 0.000 description 1
• 210000002418 meninge Anatomy 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect 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
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 235000019691 monocalcium phosphate Nutrition 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• LZWGPVKTDYQTAT-UHFFFAOYSA-N morpholin-4-yl-[4-[6-(1-propan-2-ylsulfonylindol-2-yl)pyrazin-2-yl]phenyl]methanone Chemical compound C=1C2=CC=CC=C2N(S(=O)(=O)C(C)C)C=1C(N=1)=CN=CC=1C(C=C1)=CC=C1C(=O)N1CCOCC1 LZWGPVKTDYQTAT-UHFFFAOYSA-N 0.000 description 1
• 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• 208000009091 myxoma Diseases 0.000 description 1
• ULDIVZQLPBUHAG-UHFFFAOYSA-N n',n',2,2-tetramethylpropane-1,3-diamine Chemical compound CN(C)CC(C)(C)CN ULDIVZQLPBUHAG-UHFFFAOYSA-N 0.000 description 1
• PVFIKWLTVKSXED-UHFFFAOYSA-N n'-benzyl-n,n'-dimethylethane-1,2-diamine Chemical compound CNCCN(C)CC1=CC=CC=C1 PVFIKWLTVKSXED-UHFFFAOYSA-N 0.000 description 1
• SORARJZLMNRBAQ-UHFFFAOYSA-N n,n',n'-trimethylpropane-1,3-diamine Chemical compound CNCCCN(C)C SORARJZLMNRBAQ-UHFFFAOYSA-N 0.000 description 1
• TVQYLBWVRBQOGI-UHFFFAOYSA-N n,n-dimethyl-1-piperidin-2-ylmethanamine Chemical compound CN(C)CC1CCCCN1 TVQYLBWVRBQOGI-UHFFFAOYSA-N 0.000 description 1
• AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 description 1
• UGOJBVXTCWYKAB-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCO)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 UGOJBVXTCWYKAB-UHFFFAOYSA-N 0.000 description 1
• ZTISWCXLXLMLLY-UHFFFAOYSA-N n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NCCN1CCCC1 ZTISWCXLXLMLLY-UHFFFAOYSA-N 0.000 description 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
• QEURDHGTNAIXAB-UHFFFAOYSA-N n-(azetidin-3-yl)-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C(NC=2N=C(C=NC=2)C=2NC3=CC=C(F)C=C3C=2)C(OC)=CC=1C(=O)NC1CNC1 QEURDHGTNAIXAB-UHFFFAOYSA-N 0.000 description 1
• ULIMCJSUTRFRIF-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-2-fluoro-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]benzamide Chemical compound C1=C(F)C(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 ULIMCJSUTRFRIF-UHFFFAOYSA-N 0.000 description 1
• TUFZKMOHNIDRAG-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-4-[[6-(1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 TUFZKMOHNIDRAG-UHFFFAOYSA-N 0.000 description 1
• VMYWTSYLWFVGBT-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-4-[[6-(5-fluoro-1h-indol-2-yl)pyrazin-2-yl]amino]-3-methoxybenzamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC1=CC(C(=O)NCCN(CC)CC)=CC=C1NC1=CN=CC(C=2NC3=CC=C(F)C=C3C=2)=N1 VMYWTSYLWFVGBT-UHFFFAOYSA-N 0.000 description 1
• JWJMWQRKAQBITG-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-4-[6-(1h-indol-2-yl)pyrazin-2-yl]-n-methylbenzamide Chemical compound C1=CC(C(=O)N(C)CCCN(C)C)=CC=C1C1=CN=CC(C=2NC3=CC=CC=C3C=2)=N1 JWJMWQRKAQBITG-UHFFFAOYSA-N 0.000 description 1
• FVLVBVSILSHUAF-UHFFFAOYSA-N n-benzyl-3,5-dimethyl-n-propan-2-ylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(C(C)C)CC1=CC=CC=C1 FVLVBVSILSHUAF-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000008026 nephroblastoma Diseases 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 208000003388 osteoid osteoma Diseases 0.000 description 1
• 208000008798 osteoma Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 208000021255 pancreatic insulinoma Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000008447 perception Effects 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 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
• 208000024724 pineal body neoplasm Diseases 0.000 description 1
• 201000004123 pineal gland cancer Diseases 0.000 description 1
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical class CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
• 125000006308 propyl amino group Chemical group 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 208000005333 pulmonary edema Diseases 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• JPCCABPOGHLXQC-UHFFFAOYSA-N pyrazin-2-amine;2,2,2-trifluoroacetic acid Chemical compound NC1=CN=CC=N1.OC(=O)C(F)(F)F JPCCABPOGHLXQC-UHFFFAOYSA-N 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000000552 rheumatic effect Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 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 1
• 238000000926 separation method Methods 0.000 description 1
• 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
• 230000009528 severe injury Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 235000017550 sodium carbonate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 201000005671 spondyloarthropathy Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 229940032147 starch Drugs 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 201000004415 tendinitis Diseases 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
• ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
• WPGLRFGDZJSQGI-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)C1 WPGLRFGDZJSQGI-UHFFFAOYSA-N 0.000 description 1
• AKQXKEBCONUWCL-UHFFFAOYSA-N tert-butyl 3-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(N)C1 AKQXKEBCONUWCL-UHFFFAOYSA-N 0.000 description 1
• BKZRMPOYXDWHSH-UHFFFAOYSA-N tert-butyl 4-(4-bromobenzoyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)C1=CC=C(Br)C=C1 BKZRMPOYXDWHSH-UHFFFAOYSA-N 0.000 description 1
• GSHXPDVMVVLYLH-UHFFFAOYSA-N tert-butyl 5-nitroindole-1-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 GSHXPDVMVVLYLH-UHFFFAOYSA-N 0.000 description 1
• NEMXVXVJGXZDRR-UHFFFAOYSA-N tert-butyl n-(azetidin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CNC1 NEMXVXVJGXZDRR-UHFFFAOYSA-N 0.000 description 1
• DQQJBEAXSOOCPG-ZETCQYMHSA-N tert-butyl n-[(3s)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1 DQQJBEAXSOOCPG-ZETCQYMHSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• PKYJYPDHSCLTJO-UHFFFAOYSA-N tert-butyl pyrrolo[3,2-c]pyridine-1-carboxylate Chemical compound N1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 PKYJYPDHSCLTJO-UHFFFAOYSA-N 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004149 thio group Chemical group *S* 0.000 description 1
• 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 208000004371 toothache Diseases 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 208000022271 tubular adenoma Diseases 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
• 108010002164 tyrosine receptor Proteins 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 210000001635 urinary tract Anatomy 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 208000027185 varicose disease Diseases 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 208000009540 villous adenoma Diseases 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1