JP2012519678A

JP2012519678A - キナーゼ阻害剤として使用されるピロロピリミジン

キナーゼ阻害剤として使用されるピロロピリミジン Download PDF

Info

Publication number: JP2012519678A
Authority: JP; Japan
Prior art keywords: propyl; pyrimidin; pyrrolo; amide; alkyl
Prior art date: 2009-03-04
Legal status : Withdrawn

Application number

JP2011552507A

Other languages

English (en)

Japanese (ja)

Other versions

JP2012519678A5 (https=

Inventor

エドワードジャイルズマクアイヴァー

ジョアンハフ

Current Assignee

LifeArc

Original Assignee

Medical Research Council Technology

Priority date

2009-03-04

Filing date

2010-03-04

Publication date

2012-08-30

2010-03-04 Application filed by Medical Research Council Technology filed Critical Medical Research Council Technology

2012-08-30 Publication of JP2012519678A publication Critical patent/JP2012519678A/ja

2013-03-28 Publication of JP2012519678A5 publication Critical patent/JP2012519678A5/ja

Status Withdrawn legal-status Critical Current

Links

KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 title description 2
229940043355 kinase inhibitor Drugs 0.000 title 1
239000003757 phosphotransferase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 197
-1 VEG-FR Proteins 0.000 claims abstract description 162
108091000080 Phosphotransferase Proteins 0.000 claims abstract description 56
102000020233 phosphotransferase Human genes 0.000 claims abstract description 56
101000665442 Homo sapiens Serine/threonine-protein kinase TBK1 Proteins 0.000 claims abstract description 52
102100038192 Serine/threonine-protein kinase TBK1 Human genes 0.000 claims abstract description 52
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
238000000034 method Methods 0.000 claims abstract description 45
206010030348 Open-Angle Glaucoma Diseases 0.000 claims abstract description 39
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 39
201000006366 primary open angle glaucoma Diseases 0.000 claims abstract description 38
125000003118 aryl group Chemical group 0.000 claims abstract description 32
208000035475 disorder Diseases 0.000 claims abstract description 29
239000003814 drug Substances 0.000 claims abstract description 27
102000001284 I-kappa-B kinase Human genes 0.000 claims abstract description 24
108060006678 I-kappa-B kinase Proteins 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
229910052736 halogen Inorganic materials 0.000 claims abstract description 21
150000002367 halogens Chemical class 0.000 claims abstract description 21
150000003839 salts Chemical class 0.000 claims abstract description 20
108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims abstract description 19
102100036239 Cyclin-dependent kinase 2 Human genes 0.000 claims abstract description 19
102100023483 Mitogen-activated protein kinase 15 Human genes 0.000 claims abstract description 19
238000002360 preparation method Methods 0.000 claims abstract description 19
206010040070 Septic Shock Diseases 0.000 claims abstract description 18
230000036303 septic shock Effects 0.000 claims abstract description 18
101000820294 Homo sapiens Tyrosine-protein kinase Yes Proteins 0.000 claims abstract description 16
102100021788 Tyrosine-protein kinase Yes Human genes 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 15
206010028980 Neoplasm Diseases 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
201000011510 cancer Diseases 0.000 claims abstract description 14
230000000694 effects Effects 0.000 claims abstract description 14
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 11
150000002148 esters Chemical class 0.000 claims abstract description 11
208000017442 Retinal disease Diseases 0.000 claims abstract description 10
206010038923 Retinopathy Diseases 0.000 claims abstract description 10
206010020718 hyperplasia Diseases 0.000 claims abstract description 10
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 10
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 9
208000037976 chronic inflammation Diseases 0.000 claims abstract description 9
230000006020 chronic inflammation Effects 0.000 claims abstract description 9
201000008482 osteoarthritis Diseases 0.000 claims abstract description 9
201000009273 Endometriosis Diseases 0.000 claims abstract description 8
201000004681 Psoriasis Diseases 0.000 claims abstract description 8
230000002265 prevention Effects 0.000 claims abstract description 8
230000002159 abnormal effect Effects 0.000 claims abstract description 6
150000002431 hydrogen Chemical class 0.000 claims abstract description 6
101001059429 Homo sapiens MAP/microtubule affinity-regulating kinase 3 Proteins 0.000 claims abstract description 5
102100028920 MAP/microtubule affinity-regulating kinase 3 Human genes 0.000 claims abstract description 5
101000976899 Homo sapiens Mitogen-activated protein kinase 15 Proteins 0.000 claims abstract 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 23
229910052757 nitrogen Inorganic materials 0.000 claims description 21
238000003556 assay Methods 0.000 claims description 18
125000001424 substituent group Chemical group 0.000 claims description 18
229910052717 sulfur Inorganic materials 0.000 claims description 18
150000001408 amides Chemical class 0.000 claims description 17
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
CAMSUDMBGHNVCS-UHFFFAOYSA-N n-[3-[2-[(1-methylindazol-5-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C=1C=C2N(C)N=CC2=CC=1NC(N=C12)=NC=C1C=CN2CCCNC(=O)C1CCC1 CAMSUDMBGHNVCS-UHFFFAOYSA-N 0.000 claims description 16
239000001301 oxygen Substances 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 16
239000011593 sulfur Substances 0.000 claims description 16
150000001412 amines Chemical class 0.000 claims description 13
125000005843 halogen group Chemical group 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 10
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
239000000654 additive Substances 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
HXVAENCJCDIHDG-UHFFFAOYSA-N n-[3-[2-[3-(1,3-oxazol-5-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1C1=CN=CO1 HXVAENCJCDIHDG-UHFFFAOYSA-N 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
229920006395 saturated elastomer Polymers 0.000 claims description 7
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
VNYOEBQUJAUUFG-UHFFFAOYSA-N n-[3-[2-(4-morpholin-4-ylanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=C1)=CC=C1N1CCOCC1 VNYOEBQUJAUUFG-UHFFFAOYSA-N 0.000 claims description 6
UXBFGLMTWRQROK-UHFFFAOYSA-N n-[3-[2-[(1-methylpyrazol-4-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=NN(C)C=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 UXBFGLMTWRQROK-UHFFFAOYSA-N 0.000 claims description 6
RWTHBCUIXAFSTO-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclopentanecarboxamide Chemical compound C1CCCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 RWTHBCUIXAFSTO-UHFFFAOYSA-N 0.000 claims description 6
GUXLOIRKBQPSNB-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]pyrazine-2-carboxamide Chemical compound C=1N=CC=NC=1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 GUXLOIRKBQPSNB-UHFFFAOYSA-N 0.000 claims description 6
XLGHMHOCMLFSOF-UHFFFAOYSA-N n-[3-[2-[4-(1,3-oxazol-5-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=C1)=CC=C1C1=CN=CO1 XLGHMHOCMLFSOF-UHFFFAOYSA-N 0.000 claims description 6
GPQFNIZBUXAFRW-UHFFFAOYSA-N n-[3-[2-[4-(morpholine-4-carbonyl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=C1)=CC=C1C(=O)N1CCOCC1 GPQFNIZBUXAFRW-UHFFFAOYSA-N 0.000 claims description 6
CTUNVQYSBNVSSI-UHFFFAOYSA-N n-[3-[5-bromo-2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCC4)C=C(Br)C3=CN=2)=C1 CTUNVQYSBNVSSI-UHFFFAOYSA-N 0.000 claims description 6
IGXIMFJXKCORFY-UHFFFAOYSA-N 2-methyl-n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]propanamide Chemical compound N1=C2N(CCCNC(=O)C(C)C)C=CC2=CN=C1NC(C=N1)=CC=C1N1CCOCC1 IGXIMFJXKCORFY-UHFFFAOYSA-N 0.000 claims description 5
JBDXZYCZTGLKSE-UHFFFAOYSA-N 3-methyl-n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]butanamide Chemical compound N1=C2N(CCCNC(=O)CC(C)C)C=CC2=CN=C1NC(C=N1)=CC=C1N1CCOCC1 JBDXZYCZTGLKSE-UHFFFAOYSA-N 0.000 claims description 5
SIKXIUWKPGWBBF-UHFFFAOYSA-N 5-bromo-2,4-dichloropyrimidine Chemical compound ClC1=NC=C(Br)C(Cl)=N1 SIKXIUWKPGWBBF-UHFFFAOYSA-N 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
230000005764 inhibitory process Effects 0.000 claims description 5
ZDZQARUBFUYJJG-UHFFFAOYSA-N n-[3-[2-(1h-indazol-5-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=CC2=CN=C(NC=3C=C4C=NNC4=CC=3)N=C2N1CCCNC(=O)C1CCC1 ZDZQARUBFUYJJG-UHFFFAOYSA-N 0.000 claims description 5
WIAYAESMRWUSID-UHFFFAOYSA-N n-[3-[2-(3-acetamidoanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclopentanecarboxamide Chemical compound CC(=O)NC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCCC4)C=CC3=CN=2)=C1 WIAYAESMRWUSID-UHFFFAOYSA-N 0.000 claims description 5
GBMZUVCNKNAKAG-UHFFFAOYSA-N n-[3-[2-(3-cyanoanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]thiophene-2-carboxamide Chemical compound C=1C=CSC=1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC1=CC=CC(C#N)=C1 GBMZUVCNKNAKAG-UHFFFAOYSA-N 0.000 claims description 5
LJNCBWDMHFJNTM-UHFFFAOYSA-N n-[3-[2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCC4)C=CC3=CN=2)=C1 LJNCBWDMHFJNTM-UHFFFAOYSA-N 0.000 claims description 5
SQZZHXLACIZYDV-UHFFFAOYSA-N n-[3-[2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclopentanecarboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCCC4)C=CC3=CN=2)=C1 SQZZHXLACIZYDV-UHFFFAOYSA-N 0.000 claims description 5
GUTMFMYTVXOHLR-UHFFFAOYSA-N n-[3-[2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]thiophene-2-carboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C=4SC=CC=4)C=CC3=CN=2)=C1 GUTMFMYTVXOHLR-UHFFFAOYSA-N 0.000 claims description 5
IVOCKDRLDRCJKO-UHFFFAOYSA-N n-[3-[2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]thiophene-2-carboxamide Chemical compound C=1C=CSC=1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC1=CC=CN=C1 IVOCKDRLDRCJKO-UHFFFAOYSA-N 0.000 claims description 5
SOCMOEBIHDQWNA-UHFFFAOYSA-N n-[3-[2-[(1-methylindazol-6-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=C2N(C)N=CC2=CC=C1NC(N=C12)=NC=C1C=CN2CCCNC(=O)C1CCC1 SOCMOEBIHDQWNA-UHFFFAOYSA-N 0.000 claims description 5
SVMVLQNRBXGIIV-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]-1,3-thiazole-5-carboxamide Chemical compound C=1N=CSC=1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 SVMVLQNRBXGIIV-UHFFFAOYSA-N 0.000 claims description 5
HHIWINYKIMADIE-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 HHIWINYKIMADIE-UHFFFAOYSA-N 0.000 claims description 5
GKHIWUWTZSCKON-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclopropanecarboxamide Chemical compound C1CC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 GKHIWUWTZSCKON-UHFFFAOYSA-N 0.000 claims description 5
JNFZXIAPZXXSKI-UHFFFAOYSA-N n-[3-[2-[3-(2-oxopyrrolidin-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1N1CCCC1=O JNFZXIAPZXXSKI-UHFFFAOYSA-N 0.000 claims description 5
QQPOCQHJIBTSKM-UHFFFAOYSA-N n-[3-[2-[3-(pyrrolidin-1-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1CN1CCCC1 QQPOCQHJIBTSKM-UHFFFAOYSA-N 0.000 claims description 5
FFSBKFBLCYIJHD-UHFFFAOYSA-N n-[3-[2-[3-(trifluoromethyl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]thiophene-2-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C3N(CCCNC(=O)C=4SC=CC=4)C=CC3=CN=2)=C1 FFSBKFBLCYIJHD-UHFFFAOYSA-N 0.000 claims description 5
RKNAYFKFLXRTJT-UHFFFAOYSA-N n-[3-[2-[4-(2-oxopyrrolidin-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=C1)=CC=C1N1CCCC1=O RKNAYFKFLXRTJT-UHFFFAOYSA-N 0.000 claims description 5
VPPQZQLLVNZCJA-UHFFFAOYSA-N n-[3-[2-[4-[(dimethylamino)methyl]anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=CC(CN(C)C)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 VPPQZQLLVNZCJA-UHFFFAOYSA-N 0.000 claims description 5
LRUOLZVEZLNTGN-UHFFFAOYSA-N n-[3-[2-[[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(=C1)C=NN1CCN1CCOCC1 LRUOLZVEZLNTGN-UHFFFAOYSA-N 0.000 claims description 5
KRAPPMJTUWYDCP-UHFFFAOYSA-N n-[3-[2-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 KRAPPMJTUWYDCP-UHFFFAOYSA-N 0.000 claims description 5
IGUYDWCLVZNKCN-UHFFFAOYSA-N n-[3-[5-chloro-2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCC4)C=C(Cl)C3=CN=2)=C1 IGUYDWCLVZNKCN-UHFFFAOYSA-N 0.000 claims description 5
JZGLWQPJZUIYAR-UHFFFAOYSA-N n-[3-[5-chloro-2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]thiophene-2-carboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C=4SC=CC=4)C=C(Cl)C3=CN=2)=C1 JZGLWQPJZUIYAR-UHFFFAOYSA-N 0.000 claims description 5
CFYXSQVZWRIGKJ-UHFFFAOYSA-N n-[3-[5-cyano-2-(3-fluoroanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound FC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCC4)C=C(C3=CN=2)C#N)=C1 CFYXSQVZWRIGKJ-UHFFFAOYSA-N 0.000 claims description 5
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
JVTMFKNWOUPAJH-UHFFFAOYSA-N 2-cyclopentyl-n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]acetamide Chemical compound C1=CC2=CN=C(NC=3C=NC(=CC=3)N3CCOCC3)N=C2N1CCCNC(=O)CC1CCCC1 JVTMFKNWOUPAJH-UHFFFAOYSA-N 0.000 claims description 4
230000000996 additive effect Effects 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 4
125000002757 morpholinyl group Chemical group 0.000 claims description 4
NPGQUQIVGQHEAE-UHFFFAOYSA-N n-[3-[2-(3-morpholin-4-ylanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1N1CCOCC1 NPGQUQIVGQHEAE-UHFFFAOYSA-N 0.000 claims description 4
MJOYLEXXZJPKQY-UHFFFAOYSA-N n-[3-[2-(imidazo[1,2-a]pyridin-6-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=CC2=CN=C(NC3=CN4C=CN=C4C=C3)N=C2N1CCCNC(=O)C1CCC1 MJOYLEXXZJPKQY-UHFFFAOYSA-N 0.000 claims description 4
FGYCJULFFFTMCW-UHFFFAOYSA-N n-[3-[2-(pyridin-3-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC1=CC=CN=C1 FGYCJULFFFTMCW-UHFFFAOYSA-N 0.000 claims description 4
SASKQCOPYLRNPM-UHFFFAOYSA-N n-[3-[2-(quinolin-6-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=CC2=CN=C(NC=3C=C4C=CC=NC4=CC=3)N=C2N1CCCNC(=O)C1CCC1 SASKQCOPYLRNPM-UHFFFAOYSA-N 0.000 claims description 4
YMSKBSJRJRNOIR-UHFFFAOYSA-N n-[3-[2-(quinoxalin-6-ylamino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=CC2=CN=C(NC=3C=C4N=CC=NC4=CC=3)N=C2N1CCCNC(=O)C1CCC1 YMSKBSJRJRNOIR-UHFFFAOYSA-N 0.000 claims description 4
DJFDJUNGHWFJBM-UHFFFAOYSA-N n-[3-[2-[(1-ethylpyrazol-4-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=NN(CC)C=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 DJFDJUNGHWFJBM-UHFFFAOYSA-N 0.000 claims description 4
HYZFDZRTUAUVNS-UHFFFAOYSA-N n-[3-[2-[(1-methylpyrazolo[3,4-b]pyridin-5-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C=1N=C2N(C)N=CC2=CC=1NC(N=C12)=NC=C1C=CN2CCCNC(=O)C1CCC1 HYZFDZRTUAUVNS-UHFFFAOYSA-N 0.000 claims description 4
CQTLXLLUCCXTAH-UHFFFAOYSA-N n-[3-[2-[(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(N=C12)=NC=C1C=CN2CCCNC(=O)C1CCC1 CQTLXLLUCCXTAH-UHFFFAOYSA-N 0.000 claims description 4
OYOLWPLUUKRJQM-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]butanamide Chemical compound N1=C2N(CCCNC(=O)CCC)C=CC2=CN=C1NC(C=N1)=CC=C1N1CCOCC1 OYOLWPLUUKRJQM-UHFFFAOYSA-N 0.000 claims description 4
BKRCADGEPNHIPK-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclohexanecarboxamide Chemical compound C1CCCCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 BKRCADGEPNHIPK-UHFFFAOYSA-N 0.000 claims description 4
FWWONYJHCFHGNU-UHFFFAOYSA-N n-[3-[2-[3-(1,2,4-triazol-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1N1C=NC=N1 FWWONYJHCFHGNU-UHFFFAOYSA-N 0.000 claims description 4
TWPYVVZZLDOPKE-UHFFFAOYSA-N n-[3-[2-[3-(morpholin-4-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1CN1CCOCC1 TWPYVVZZLDOPKE-UHFFFAOYSA-N 0.000 claims description 4
HRCBKEBBMXSASN-UHFFFAOYSA-N n-[3-[2-[3-(piperidin-1-ylmethyl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=1)=CC=CC=1CN1CCCCC1 HRCBKEBBMXSASN-UHFFFAOYSA-N 0.000 claims description 4
UFHRYOOCKSRQMN-UHFFFAOYSA-N n-[3-[2-[4-(1,2,4-triazol-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=C1)=CC=C1N1C=NC=N1 UFHRYOOCKSRQMN-UHFFFAOYSA-N 0.000 claims description 4
HPCJOYKWJJEYJN-UHFFFAOYSA-N n-[3-[2-[4-(1-methylpiperidin-4-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(C)CCC1C(C=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 HPCJOYKWJJEYJN-UHFFFAOYSA-N 0.000 claims description 4
ANVBEYUNPJFCQV-UHFFFAOYSA-N n-[3-[2-[4-(4-cyano-1-methylpiperidin-4-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(C)CCC1(C#N)C(C=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 ANVBEYUNPJFCQV-UHFFFAOYSA-N 0.000 claims description 4
IAQZCAABGCPKQD-UHFFFAOYSA-N n-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 IAQZCAABGCPKQD-UHFFFAOYSA-N 0.000 claims description 4
DXCQLKJTTKRJSX-UHFFFAOYSA-N n-[3-[2-[[6-(4-methyl-1,4-diazepan-1-yl)pyridin-3-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(C)CCCN1C(N=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 DXCQLKJTTKRJSX-UHFFFAOYSA-N 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 4
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 3
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
VXJJQHRIKKTXEP-UHFFFAOYSA-N [(e)-2-ethoxyethenyl]tin Chemical compound CCO\C=C\[Sn] VXJJQHRIKKTXEP-UHFFFAOYSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000004537 indazol-5-yl group Chemical group N1N=CC2=CC(=CC=C12)* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
CHXSKWJFRCPDDE-UHFFFAOYSA-N n-[3-[2-[4-[1-(2-fluoroethyl)piperidin-4-yl]anilino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C1CN(CCF)CCC1C(C=C1)=CC=C1NC1=NC=C(C=CN2CCCNC(=O)C3CCC3)C2=N1 CHXSKWJFRCPDDE-UHFFFAOYSA-N 0.000 claims description 3
UIVUUYYWFTWMHH-UHFFFAOYSA-N n-[3-[5-chloro-2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound C12=NC(NC=3C=NC(=CC=3)N3CCOCC3)=NC=C2C(Cl)=CN1CCCNC(=O)C1CCC1 UIVUUYYWFTWMHH-UHFFFAOYSA-N 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
229940124597 therapeutic agent Drugs 0.000 claims description 3
125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 2
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
UNWGHJICAJXZAG-UHFFFAOYSA-N 2-cyclopropyl-n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]acetamide Chemical compound C1=CC2=CN=C(NC=3C=NC(=CC=3)N3CCOCC3)N=C2N1CCCNC(=O)CC1CC1 UNWGHJICAJXZAG-UHFFFAOYSA-N 0.000 claims description 2
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
IIHXGROJAPUAGM-UHFFFAOYSA-N n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]oxolane-3-carboxamide Chemical compound C1COCC1C(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 IIHXGROJAPUAGM-UHFFFAOYSA-N 0.000 claims description 2
NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
208000025298 Alzheimer disease 15 Diseases 0.000 claims 2
208000012920 Alzheimer disease without neurofibrillary tangles Diseases 0.000 claims 2
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
208000024827 Alzheimer disease Diseases 0.000 abstract description 8
208000032170 Congenital Abnormalities Diseases 0.000 abstract description 2
206010061619 Deformity Diseases 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
239000000203 mixture Substances 0.000 description 89
239000000543 intermediate Substances 0.000 description 49
239000007787 solid Substances 0.000 description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
238000005481 NMR spectroscopy Methods 0.000 description 37
239000000047 product Substances 0.000 description 37
239000000243 solution Substances 0.000 description 35
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
238000009472 formulation Methods 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
238000000746 purification Methods 0.000 description 26
235000002639 sodium chloride Nutrition 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
201000010099 disease Diseases 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
235000019439 ethyl acetate Nutrition 0.000 description 18
102100031822 Optineurin Human genes 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 17
239000003446 ligand Substances 0.000 description 17
239000007788 liquid Substances 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
101710109276 Mitogen-activated protein kinase 15 Proteins 0.000 description 15
239000002904 solvent Substances 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
102000001253 Protein Kinase Human genes 0.000 description 14
238000004440 column chromatography Methods 0.000 description 14
108060006633 protein kinase Proteins 0.000 description 14
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
239000000706 filtrate Substances 0.000 description 13
230000027455 binding Effects 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
238000010992 reflux Methods 0.000 description 12
210000004027 cell Anatomy 0.000 description 11
239000003921 oil Substances 0.000 description 11
239000006174 pH buffer Substances 0.000 description 11
108090000623 proteins and genes Proteins 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000013543 active substance Substances 0.000 description 10
229940079593 drug Drugs 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
239000003826 tablet Substances 0.000 description 10
230000001225 therapeutic effect Effects 0.000 description 10
101000992283 Homo sapiens Optineurin Proteins 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
239000000839 emulsion Substances 0.000 description 9
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
101710131459 Optineurin Proteins 0.000 description 8
239000012298 atmosphere Substances 0.000 description 8
239000002775 capsule Substances 0.000 description 8
239000000969 carrier Substances 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
239000012043 crude product Substances 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
239000000843 powder Substances 0.000 description 7
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
239000012267 brine Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000006071 cream Substances 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
230000003993 interaction Effects 0.000 description 6
239000010410 layer Substances 0.000 description 6
239000000314 lubricant Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
239000003755 preservative agent Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000000758 substrate Substances 0.000 description 6
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
108010032038 Interferon Regulatory Factor-3 Proteins 0.000 description 5
102100029843 Interferon regulatory factor 3 Human genes 0.000 description 5
206010067013 Normal tension glaucoma Diseases 0.000 description 5
102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 5
108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
230000004913 activation Effects 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
239000011230 binding agent Substances 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229940014259 gelatin Drugs 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
201000002978 low tension glaucoma Diseases 0.000 description 5
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 5
238000000465 moulding Methods 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 4
102000004127 Cytokines Human genes 0.000 description 4
108090000695 Cytokines Proteins 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
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 4
108010070675 Glutathione transferase Proteins 0.000 description 4
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 4
101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 4
235000010643 Leucaena leucocephala Nutrition 0.000 description 4
240000007472 Leucaena leucocephala Species 0.000 description 4
102000019149 MAP kinase activity proteins Human genes 0.000 description 4
108040008097 MAP kinase activity proteins Proteins 0.000 description 4
102100033610 MAP kinase-interacting serine/threonine-protein kinase 2 Human genes 0.000 description 4
101710138999 MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 description 4
235000019502 Orange oil Nutrition 0.000 description 4
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 4
239000005441 aurora Substances 0.000 description 4
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 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
238000004113 cell culture Methods 0.000 description 4
230000004663 cell proliferation Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000007906 compression Methods 0.000 description 4
230000006835 compression Effects 0.000 description 4
238000013270 controlled release Methods 0.000 description 4
229910001873 dinitrogen Inorganic materials 0.000 description 4
239000000284 extract Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
229960001031 glucose Drugs 0.000 description 4
239000008187 granular material Substances 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
230000000155 isotopic effect Effects 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
108020001756 ligand binding domains Proteins 0.000 description 4
238000002156 mixing Methods 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
230000035772 mutation Effects 0.000 description 4
230000004770 neurodegeneration Effects 0.000 description 4
208000015122 neurodegenerative disease Diseases 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000010502 orange oil Substances 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
239000000651 prodrug Substances 0.000 description 4
229940002612 prodrug Drugs 0.000 description 4
239000003909 protein kinase inhibitor Substances 0.000 description 4
239000001632 sodium acetate Substances 0.000 description 4
235000017281 sodium acetate Nutrition 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
229960004793 sucrose Drugs 0.000 description 4
239000004094 surface-active agent Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
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 4
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
GQPLQVMAOCKIHC-UHFFFAOYSA-N 4-(4-bromophenyl)-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CC=C(Br)C=C1 GQPLQVMAOCKIHC-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
241000416162 Astragalus gummifer Species 0.000 description 3
206010006187 Breast cancer Diseases 0.000 description 3
208000026310 Breast neoplasm Diseases 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
239000007821 HATU Substances 0.000 description 3
241000282412 Homo Species 0.000 description 3
101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 3
101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 3
101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 3
102000003996 Interferon-beta Human genes 0.000 description 3
108090000467 Interferon-beta Proteins 0.000 description 3
102000004890 Interleukin-8 Human genes 0.000 description 3
108090001007 Interleukin-8 Proteins 0.000 description 3
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
108010045717 Proto-Oncogene Proteins c-akt Proteins 0.000 description 3
206010037211 Psychomotor hyperactivity Diseases 0.000 description 3
229920002684 Sepharose Polymers 0.000 description 3
229910004298 SiO 2 Inorganic materials 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
102100039360 Toll-like receptor 4 Human genes 0.000 description 3
229920001615 Tragacanth Polymers 0.000 description 3
208000025865 Ulcer Diseases 0.000 description 3
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
206010052428 Wound Diseases 0.000 description 3
208000027418 Wounds and injury Diseases 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
230000008859 change Effects 0.000 description 3
238000012875 competitive assay Methods 0.000 description 3
JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 3
239000008121 dextrose Substances 0.000 description 3
SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000002158 endotoxin Substances 0.000 description 3
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
235000013355 food flavoring agent Nutrition 0.000 description 3
239000012458 free base Substances 0.000 description 3
238000013537 high throughput screening Methods 0.000 description 3
230000006698 induction Effects 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
239000002198 insoluble material Substances 0.000 description 3
229960001388 interferon-beta Drugs 0.000 description 3
238000007918 intramuscular administration Methods 0.000 description 3
239000008101 lactose Substances 0.000 description 3
229960001375 lactose Drugs 0.000 description 3
229920006008 lipopolysaccharide Polymers 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
APUMXNXTKMIWCL-UHFFFAOYSA-N n-[3-[2-(3-acetamidoanilino)pyrrolo[2,3-d]pyrimidin-7-yl]propyl]cyclobutanecarboxamide Chemical compound CC(=O)NC1=CC=CC(NC=2N=C3N(CCCNC(=O)C4CCC4)C=CC3=CN=2)=C1 APUMXNXTKMIWCL-UHFFFAOYSA-N 0.000 description 3
210000004498 neuroglial cell Anatomy 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000002245 particle Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
238000002953 preparative HPLC Methods 0.000 description 3
239000003380 propellant Substances 0.000 description 3
230000000069 prophylactic effect Effects 0.000 description 3
230000002685 pulmonary effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
229940032147 starch Drugs 0.000 description 3
150000003460 sulfonic acids Chemical class 0.000 description 3
239000000829 suppository Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
235000010487 tragacanth Nutrition 0.000 description 3
239000000196 tragacanth Substances 0.000 description 3
229940116362 tragacanth Drugs 0.000 description 3
231100000397 ulcer Toxicity 0.000 description 3
238000005406 washing Methods 0.000 description 3
QQQZEFAUOMUXLS-UHFFFAOYSA-N (1-diphenylphosphanyl-9,9-dimethylxanthen-2-yl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C1=C2C(C)(C)C3=CC=CC=C3OC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QQQZEFAUOMUXLS-UHFFFAOYSA-N 0.000 description 2
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
SWJPEBQEEAHIGZ-UHFFFAOYSA-N 1,4-dibromobenzene Chemical compound BrC1=CC=C(Br)C=C1 SWJPEBQEEAHIGZ-UHFFFAOYSA-N 0.000 description 2
WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 2
OTBMNUJANDVYRB-UHFFFAOYSA-N 1-(2-fluoroethyl)-4-(4-nitrophenyl)piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1CCN(CCF)CC1 OTBMNUJANDVYRB-UHFFFAOYSA-N 0.000 description 2
PRGFHJTXOUUKAQ-UHFFFAOYSA-N 1-methyl-4-(5-nitropyridin-2-yl)-1,4-diazepane Chemical compound C1CN(C)CCCN1C1=CC=C([N+]([O-])=O)C=N1 PRGFHJTXOUUKAQ-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
XAKLATSIXCJUEU-UHFFFAOYSA-N 2-[4-(4-nitrophenyl)piperidin-1-yl]ethanol Chemical compound C1CN(CCO)CCC1C1=CC=C([N+]([O-])=O)C=C1 XAKLATSIXCJUEU-UHFFFAOYSA-N 0.000 description 2
KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
LPAOKBRALMIGDO-UHFFFAOYSA-N 4-(4-bromophenyl)-1-methylpiperidine-4-carbonitrile Chemical compound C1CN(C)CCC1(C#N)C1=CC=C(Br)C=C1 LPAOKBRALMIGDO-UHFFFAOYSA-N 0.000 description 2
DYPSVXOHODYAKW-UHFFFAOYSA-N 4-(4-bromophenyl)-4-fluoro-1-methylpiperidine Chemical compound C1CN(C)CCC1(F)C1=CC=C(Br)C=C1 DYPSVXOHODYAKW-UHFFFAOYSA-N 0.000 description 2
MVFDBFPPEXUCFG-UHFFFAOYSA-N 4-[4-(benzhydrylideneamino)phenyl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CC=C(N=C(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 MVFDBFPPEXUCFG-UHFFFAOYSA-N 0.000 description 2
IZXZXHIPACYSDO-UHFFFAOYSA-N 4-[4-(benzhydrylideneamino)phenyl]-1-methylpiperidine-4-carbonitrile Chemical compound C1CN(C)CCC1(C#N)C1=CC=C(N=C(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 IZXZXHIPACYSDO-UHFFFAOYSA-N 0.000 description 2
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
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 description 2
VVTSPTCBHTWXMD-UHFFFAOYSA-N 6-morpholin-4-ylpyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCOCC1 VVTSPTCBHTWXMD-UHFFFAOYSA-N 0.000 description 2
229920000936 Agarose Polymers 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
208000023275 Autoimmune disease Diseases 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
101710165567 Extracellular signal-regulated kinase 1 Proteins 0.000 description 2
206010016654 Fibrosis Diseases 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
241000238631 Hexapoda Species 0.000 description 2
101000576802 Homo sapiens Mesothelin Proteins 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
102000002227 Interferon Type I Human genes 0.000 description 2
108010014726 Interferon Type I Proteins 0.000 description 2
108010002352 Interleukin-1 Proteins 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
206010058467 Lung neoplasm malignant Diseases 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
102000047918 Myelin Basic Human genes 0.000 description 2
101710107068 Myelin basic protein Proteins 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
206010060862 Prostate cancer Diseases 0.000 description 2
208000000236 Prostatic Neoplasms Diseases 0.000 description 2
101150093978 RALB gene Proteins 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
108010060804 Toll-Like Receptor 4 Proteins 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
238000001042 affinity chromatography Methods 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
238000010171 animal model Methods 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
230000006907 apoptotic process Effects 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
229960005070 ascorbic acid Drugs 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
230000001580 bacterial effect Effects 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
125000005605 benzo group Chemical group 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
CDZMEDUUZXFNNI-UHFFFAOYSA-N benzyl n-[3-(2-chloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]carbamate Chemical compound C12=NC(Cl)=NC=C2C=CN1CCCNC(=O)OCC1=CC=CC=C1 CDZMEDUUZXFNNI-UHFFFAOYSA-N 0.000 description 2
UPRGFDSZUNDTJH-XFXZXTDPSA-N benzyl n-[3-[[2-chloro-5-[(z)-2-ethoxyethenyl]pyrimidin-4-yl]amino]propyl]carbamate Chemical compound CCO\C=C/C1=CN=C(Cl)N=C1NCCCNC(=O)OCC1=CC=CC=C1 UPRGFDSZUNDTJH-XFXZXTDPSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000024245 cell differentiation Effects 0.000 description 2
230000010261 cell growth Effects 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
239000003405 delayed action preparation Substances 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
229910052805 deuterium Inorganic materials 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
150000001991 dicarboxylic acids Chemical class 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000009826 distribution Methods 0.000 description 2
229940000406 drug candidate Drugs 0.000 description 2
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
230000004761 fibrosis Effects 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
208000014829 head and neck neoplasm Diseases 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
229940071870 hydroiodic acid Drugs 0.000 description 2
150000004679 hydroxides Chemical class 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
239000012535 impurity Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
229940096397 interleukin-8 Drugs 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
201000005202 lung cancer Diseases 0.000 description 2
208000020816 lung neoplasm Diseases 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
229960001855 mannitol Drugs 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
230000010534 mechanism of action Effects 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
229960002900 methylcellulose Drugs 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000007932 molded tablet Substances 0.000 description 2
SKFGDPDEGVIRBI-UHFFFAOYSA-N n-(3-aminopropyl)cyclobutanecarboxamide;hydrochloride Chemical compound Cl.NCCCNC(=O)C1CCC1 SKFGDPDEGVIRBI-UHFFFAOYSA-N 0.000 description 2
CEDAJPHRKFFUBY-UHFFFAOYSA-N n-[3-(2-chloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]cyclobutanecarboxamide Chemical compound C12=NC(Cl)=NC=C2C=CN1CCCNC(=O)C1CCC1 CEDAJPHRKFFUBY-UHFFFAOYSA-N 0.000 description 2
QCZGHGIKOQTXRK-JXMROGBWSA-N n-[3-[[2-chloro-5-[(e)-2-ethoxyethenyl]pyrimidin-4-yl]amino]propyl]cyclobutanecarboxamide Chemical compound CCO\C=C\C1=CN=C(Cl)N=C1NCCCNC(=O)C1CCC1 QCZGHGIKOQTXRK-JXMROGBWSA-N 0.000 description 2
WZWXHLVBLAFEDT-UHFFFAOYSA-N n-[4-(4-fluoro-1-methylpiperidin-4-yl)phenyl]-1,1-diphenylmethanimine Chemical compound C1CN(C)CCC1(F)C1=CC=C(N=C(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 WZWXHLVBLAFEDT-UHFFFAOYSA-N 0.000 description 2
210000003733 optic disk Anatomy 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
230000037361 pathway Effects 0.000 description 2
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
230000008569 process Effects 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
230000000770 proinflammatory effect Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
102200153977 rs28939688 Human genes 0.000 description 2
238000012216 screening Methods 0.000 description 2
238000007493 shaping process Methods 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
229960002920 sorbitol Drugs 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
238000012799 strong cation exchange Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
230000001960 triggered effect Effects 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
230000009385 viral infection Effects 0.000 description 2
WEHVQIQNGXWTME-UHFFFAOYSA-N (4-aminophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CCOCC1 WEHVQIQNGXWTME-UHFFFAOYSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
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 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
AMDUVBKOPJXBBN-UHFFFAOYSA-N 1-(2-morpholin-4-ylethyl)pyrazol-4-amine Chemical compound C1=C(N)C=NN1CCN1CCOCC1 AMDUVBKOPJXBBN-UHFFFAOYSA-N 0.000 description 1
IOMOVAPYJQVJDK-UHFFFAOYSA-N 1-(4-aminophenyl)pyrrolidin-2-one Chemical compound C1=CC(N)=CC=C1N1C(=O)CCC1 IOMOVAPYJQVJDK-UHFFFAOYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
PYOFNPHTKBSXOM-UHFFFAOYSA-N 1-methylindazol-5-amine Chemical compound NC1=CC=C2N(C)N=CC2=C1 PYOFNPHTKBSXOM-UHFFFAOYSA-N 0.000 description 1
HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 1
XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 1
MFHFWRBXPQDZSA-UHFFFAOYSA-N 2-(4-bromophenyl)acetonitrile Chemical compound BrC1=CC=C(CC#N)C=C1 MFHFWRBXPQDZSA-UHFFFAOYSA-N 0.000 description 1
ADHAUWMNDHMUMH-UHFFFAOYSA-L 2-[bis(carboxylatomethyl)amino]acetate;hydron;nickel(2+) Chemical compound [Ni+2].OC(=O)CN(CC([O-])=O)CC([O-])=O ADHAUWMNDHMUMH-UHFFFAOYSA-L 0.000 description 1
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
BAZVFQBTJPBRTJ-UHFFFAOYSA-N 2-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1 BAZVFQBTJPBRTJ-UHFFFAOYSA-N 0.000 description 1
KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
LUDAHKXAGRYZCE-UHFFFAOYSA-N 2-ethoxyethenylstannane Chemical compound CCOC=C[SnH3] LUDAHKXAGRYZCE-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
108010082078 3-Phosphoinositide-Dependent Protein Kinases Proteins 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
SLJBMRSOKUTXDF-UHFFFAOYSA-N 4-(1,3-oxazol-5-yl)aniline Chemical compound C1=CC(N)=CC=C1C1=CN=CO1 SLJBMRSOKUTXDF-UHFFFAOYSA-N 0.000 description 1
ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
SDHFOJKCQMQFEP-UHFFFAOYSA-N 4-(4-aminophenyl)-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CC=C(N)C=C1 SDHFOJKCQMQFEP-UHFFFAOYSA-N 0.000 description 1
DBPJFMIHBWIVRX-UHFFFAOYSA-N 4-(4-aminophenyl)-1-methylpiperidine-4-carbonitrile Chemical compound C1CN(C)CCC1(C#N)C1=CC=C(N)C=C1 DBPJFMIHBWIVRX-UHFFFAOYSA-N 0.000 description 1
NTRDVTAJGZYPQJ-UHFFFAOYSA-N 4-(4-methoxy-1-methylpiperidin-4-yl)aniline Chemical compound C=1C=C(N)C=CC=1C1(OC)CCN(C)CC1 NTRDVTAJGZYPQJ-UHFFFAOYSA-N 0.000 description 1
CDSJZBOLNDWPAA-UHFFFAOYSA-N 4-(4-nitrophenyl)piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1CCNCC1 CDSJZBOLNDWPAA-UHFFFAOYSA-N 0.000 description 1
ZJDBQMWMDZEONW-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C(O)=O)C=C1 ZJDBQMWMDZEONW-UHFFFAOYSA-N 0.000 description 1
YUCBLVFHJWOYDN-PPIALRKJSA-N 4-[(r)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-1-[(r)-[(2r,4r,5s)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@@H](OC=3C4=CC=CC=C4C(O[C@@H]([C@@H]4N5CC[C@@H]([C@@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-PPIALRKJSA-N 0.000 description 1
XNWLZCTXKRXFFC-UHFFFAOYSA-N 4-[1-(2-fluoroethyl)piperidin-4-yl]aniline Chemical compound C1=CC(N)=CC=C1C1CCN(CCF)CC1 XNWLZCTXKRXFFC-UHFFFAOYSA-N 0.000 description 1
VYWULEPJDHQXQG-UHFFFAOYSA-N 4-[2-(4-nitropyrazol-1-yl)ethyl]morpholine Chemical compound C1=C([N+](=O)[O-])C=NN1CCN1CCOCC1 VYWULEPJDHQXQG-UHFFFAOYSA-N 0.000 description 1
RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
QSJJDPGQZUUPSZ-UHFFFAOYSA-N 4-morpholin-4-ylpyridin-3-amine Chemical compound NC1=CN=CC=C1N1CCOCC1 QSJJDPGQZUUPSZ-UHFFFAOYSA-N 0.000 description 1
XORHNJQEWQGXCN-UHFFFAOYSA-N 4-nitro-1h-pyrazole Chemical compound [O-][N+](=O)C=1C=NNC=1 XORHNJQEWQGXCN-UHFFFAOYSA-N 0.000 description 1
XPHXRUWQUMDDGT-UHFFFAOYSA-N 5-(2-ethoxyethenyl)pyrimidine Chemical compound CCOC=CC1=CN=CN=C1 XPHXRUWQUMDDGT-UHFFFAOYSA-N 0.000 description 1
GYCPLYCTMDTEPU-UHFFFAOYSA-N 5-bromopyrimidine Chemical compound BrC1=CN=CN=C1 GYCPLYCTMDTEPU-UHFFFAOYSA-N 0.000 description 1
YYWHTZQHQXNZLD-UHFFFAOYSA-N 6-(4-methyl-1,4-diazepan-1-yl)pyridin-3-amine Chemical compound C1CN(C)CCCN1C1=CC=C(N)C=N1 YYWHTZQHQXNZLD-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
SEDJZVZSEVOYCT-UHFFFAOYSA-N 7-(3-aminopropyl)-n-(6-morpholin-4-ylpyridin-3-yl)pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound N1=C2N(CCCN)C=CC2=CN=C1NC(C=N1)=CC=C1N1CCOCC1 SEDJZVZSEVOYCT-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
101001082110 Acanthamoeba polyphaga mimivirus Eukaryotic translation initiation factor 4E homolog Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010003571 Astrocytoma Diseases 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
239000007848 Bronsted acid Substances 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
102000001327 Chemokine CCL5 Human genes 0.000 description 1
108010055166 Chemokine CCL5 Proteins 0.000 description 1
102000019034 Chemokines Human genes 0.000 description 1
108010012236 Chemokines Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
108010060273 Cyclin A2 Proteins 0.000 description 1
102100025191 Cyclin-A2 Human genes 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
101001082109 Danio rerio Eukaryotic translation initiation factor 4E-1B Proteins 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
101001031598 Dictyostelium discoideum Probable serine/threonine-protein kinase fhkC Proteins 0.000 description 1
102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 1
102100023332 Dual specificity mitogen-activated protein kinase kinase 7 Human genes 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
101150057924 Exoc2 gene Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
108010093488 His-His-His-His-His-His Proteins 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 1
101000624594 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 7 Proteins 0.000 description 1
101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 1
101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 1
101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
102000019145 JUN kinase activity proteins Human genes 0.000 description 1
208000007766 Kaposi sarcoma Diseases 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
102000043136 MAP kinase family Human genes 0.000 description 1
108091054455 MAP kinase family Proteins 0.000 description 1
108700012928 MAPK14 Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
102000003945 NF-kappa B Human genes 0.000 description 1
108010057466 NF-kappa B Proteins 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
108700011066 PreScission Protease Proteins 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
229940116193 Protein phosphatase inhibitor Drugs 0.000 description 1
102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 1
102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
108020004459 Small interfering RNA Proteins 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
206010057644 Testis cancer Diseases 0.000 description 1
208000024770 Thyroid neoplasm Diseases 0.000 description 1
102100024324 Toll-like receptor 3 Human genes 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
102100040247 Tumor necrosis factor Human genes 0.000 description 1
102000009270 Tumour necrosis factor alpha Human genes 0.000 description 1
108050000101 Tumour necrosis factor alpha Proteins 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
FSAVDKDHPDSCTO-WQLSENKSSA-N [(z)-2-chloro-1-(2,4-dichlorophenyl)ethenyl] diethyl phosphate Chemical compound CCOP(=O)(OCC)O\C(=C/Cl)C1=CC=C(Cl)C=C1Cl FSAVDKDHPDSCTO-WQLSENKSSA-N 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
238000013019 agitation Methods 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
239000001099 ammonium carbonate Substances 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
230000003321 amplification Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000002870 angiogenesis inducing agent Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
229960004977 anhydrous lactose Drugs 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000005362 aryl sulfone group Chemical group 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
XKMBTMXQMDLSRB-UHFFFAOYSA-N benzyl n-(3-aminopropyl)carbamate;hydron;chloride Chemical compound Cl.NCCCNC(=O)OCC1=CC=CC=C1 XKMBTMXQMDLSRB-UHFFFAOYSA-N 0.000 description 1
KTEWYIJQUKJYOO-UHFFFAOYSA-N benzyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound ClC1=NC=C(Br)C(NCCCNC(=O)OCC=2C=CC=CC=2)=N1 KTEWYIJQUKJYOO-UHFFFAOYSA-N 0.000 description 1
HYMCQHWCIXRDCB-UHFFFAOYSA-N benzyl n-[3-[2-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrrolo[2,3-d]pyrimidin-7-yl]propyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NCCCN(C1=N2)C=CC1=CN=C2NC(C=N1)=CC=C1N1CCOCC1 HYMCQHWCIXRDCB-UHFFFAOYSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group 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
238000004166 bioassay Methods 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000036765 blood level Effects 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
229940105329 carboxymethylcellulose Drugs 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
229940044683 chemotherapy drug Drugs 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
150000001805 chlorine compounds Chemical group 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
208000010877 cognitive disease Diseases 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000006552 constitutive activation Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-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
230000007123 defense Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
230000001934 delay Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
210000004207 dermis Anatomy 0.000 description 1
150000001975 deuterium Chemical group 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical group ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
238000007878 drug screening assay Methods 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
239000000975 dye Substances 0.000 description 1
235000006694 eating habits Nutrition 0.000 description 1
239000012636 effector Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
230000029142 excretion Effects 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
150000004675 formic acid derivatives Chemical class 0.000 description 1
239000012634 fragment Substances 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
229960005150 glycerol Drugs 0.000 description 1
230000012010 growth Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
230000002706 hydrostatic effect Effects 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000002513 implantation Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003999 initiator Substances 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
210000005007 innate immune system Anatomy 0.000 description 1
229910001853 inorganic hydroxide Inorganic materials 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229940079322 interferon Drugs 0.000 description 1
230000010468 interferon response Effects 0.000 description 1
230000011542 interferon-beta production Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 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
238000002955 isolation Methods 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
229960000829 kaolin Drugs 0.000 description 1
238000000021 kinase assay Methods 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
201000007270 liver cancer Diseases 0.000 description 1
208000014018 liver neoplasm Diseases 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
239000011654 magnesium acetate Substances 0.000 description 1
235000011285 magnesium acetate Nutrition 0.000 description 1
229940069446 magnesium acetate Drugs 0.000 description 1
229940057948 magnesium stearate Drugs 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
229940049920 malate Drugs 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
208000026037 malignant tumor of neck Diseases 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
231100000682 maximum tolerated dose Toxicity 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
UHNSRFWQBVXBSK-UHFFFAOYSA-N methanol;2,2,2-trifluoroacetic acid Chemical compound OC.OC(=O)C(F)(F)F UHNSRFWQBVXBSK-UHFFFAOYSA-N 0.000 description 1
GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 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
210000004688 microtubule Anatomy 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
239000003595 mist Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
239000002324 mouth wash Substances 0.000 description 1
229940051866 mouthwash Drugs 0.000 description 1
XWJFCSJKVLJVOB-UHFFFAOYSA-N n-[3-(2,5-dichloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]thiophene-2-carboxamide Chemical compound C12=NC(Cl)=NC=C2C(Cl)=CN1CCCNC(=O)C1=CC=CS1 XWJFCSJKVLJVOB-UHFFFAOYSA-N 0.000 description 1
MMUONRPNLCMTML-UHFFFAOYSA-N n-[3-(2-chloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]cyclopentanecarboxamide Chemical compound C12=NC(Cl)=NC=C2C=CN1CCCNC(=O)C1CCCC1 MMUONRPNLCMTML-UHFFFAOYSA-N 0.000 description 1
SNLRFIXUKOFGBI-UHFFFAOYSA-N n-[3-(2-chloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]thiophene-2-carboxamide Chemical compound C12=NC(Cl)=NC=C2C=CN1CCCNC(=O)C1=CC=CS1 SNLRFIXUKOFGBI-UHFFFAOYSA-N 0.000 description 1
LYDPXOSSNONDHZ-UHFFFAOYSA-N n-[3-(5-bromo-2-chloropyrrolo[2,3-d]pyrimidin-7-yl)propyl]cyclobutanecarboxamide Chemical compound C12=NC(Cl)=NC=C2C(Br)=CN1CCCNC(=O)C1CCC1 LYDPXOSSNONDHZ-UHFFFAOYSA-N 0.000 description 1
UHFIANLFSZHHSH-UHFFFAOYSA-N n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]cyclobutanecarboxamide Chemical compound ClC1=NC=C(Br)C(NCCCNC(=O)C2CCC2)=N1 UHFIANLFSZHHSH-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
210000003928 nasal cavity Anatomy 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
210000001331 nose Anatomy 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 1
VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 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
229940023569 palmate Drugs 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
208000003154 papilloma Diseases 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
235000020030 perry Nutrition 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
150000004633 phorbol derivatives Chemical class 0.000 description 1
239000002644 phorbol ester Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
150000003906 phosphoinositides Chemical class 0.000 description 1
239000003934 phosphoprotein phosphatase inhibitor Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
YXJYBPXSEKMEEJ-UHFFFAOYSA-N phosphoric acid;sulfuric acid Chemical compound OP(O)(O)=O.OS(O)(=O)=O YXJYBPXSEKMEEJ-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
239000006187 pill Substances 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000001023 pro-angiogenic effect Effects 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
108010007439 proline transporter Proteins 0.000 description 1
239000001294 propane Substances 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000013014 purified material Substances 0.000 description 1
NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000012207 quantitative assay Methods 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000020874 response to hypoxia Effects 0.000 description 1
210000003994 retinal ganglion cell Anatomy 0.000 description 1
238000012552 review Methods 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007789 sealing Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
POHWAQLZBIMPRN-UHFFFAOYSA-N tert-butyl n-(3-aminopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCN POHWAQLZBIMPRN-UHFFFAOYSA-N 0.000 description 1
MTANXWKGEMQTHK-UHFFFAOYSA-N tert-butyl n-[4-(morpholine-4-carbonyl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C(=O)N1CCOCC1 MTANXWKGEMQTHK-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
201000003120 testicular cancer Diseases 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
WARKYKQCOXTIAO-UHFFFAOYSA-N tributyl(2-ethoxyethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)\C=C/OCC WARKYKQCOXTIAO-UHFFFAOYSA-N 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
125000005500 uronium group Chemical group 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
238000007738 vacuum evaporation Methods 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
239000013598 vector Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229940045860 white wax Drugs 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1