TWI430798B - 猬狀途徑之抑制劑，其製備方法，包含彼等之組合物及其用途 - Google Patents

Info

Publication number

TWI430798B

TWI430798B TW097109202A TW97109202A TWI430798B TW I430798 B TWI430798 B TW I430798B TW 097109202 A TW097109202 A TW 097109202A TW 97109202 A TW97109202 A TW 97109202A TW I430798 B TWI430798 B TW I430798B

Authority

TW

Taiwan

Prior art keywords

group

amino

compound

methyl

formula

Prior art date

2007-03-14

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000203 mixture Substances 0.000 title claims description 52
• 230000037361 pathway Effects 0.000 title claims description 20
• 238000002360 preparation method Methods 0.000 title claims description 7
• 239000003112 inhibitor Substances 0.000 title description 2
• 241000289669 Erinaceus europaeus Species 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 780
• 125000000217 alkyl group Chemical group 0.000 claims description 573
• -1 pyrido[3,2-d]pyrimidinyl Chemical group 0.000 claims description 434
• 229910052739 hydrogen Inorganic materials 0.000 claims description 319
• 239000001257 hydrogen Substances 0.000 claims description 319
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 242
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 213
• 125000001072 heteroaryl group Chemical group 0.000 claims description 170
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 157
• 150000003839 salts Chemical class 0.000 claims description 104
• 125000005843 halogen group Chemical group 0.000 claims description 101
• 125000003545 alkoxy group Chemical group 0.000 claims description 94
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 92
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 84
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 82
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 80
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 71
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 68
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 65
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 62
• 206010028980 Neoplasm Diseases 0.000 claims description 60
• 125000001188 haloalkyl group Chemical group 0.000 claims description 58
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 56
• 125000003282 alkyl amino group Chemical group 0.000 claims description 52
• 150000001412 amines Chemical class 0.000 claims description 48
• 201000011510 cancer Diseases 0.000 claims description 44
• 125000001424 substituent group Chemical group 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 39
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 39
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 37
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 36
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 32
• 238000000034 method Methods 0.000 claims description 32
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 31
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 29
• 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 28
• 239000012453 solvate Substances 0.000 claims description 28
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 27
• 201000010099 disease Diseases 0.000 claims description 27
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 20
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
• 125000003277 amino group Chemical group 0.000 claims description 18
• 125000005122 aminoalkylamino group Chemical group 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 17
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 16
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 14
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
• 150000001335 aliphatic alkanes Chemical group 0.000 claims description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
• 125000006413 ring segment Chemical group 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
• 125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 11
• 125000002619 bicyclic group Chemical group 0.000 claims description 11
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 238000011282 treatment Methods 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
• 125000004122 cyclic group Chemical group 0.000 claims description 10
• 229920006395 saturated elastomer Polymers 0.000 claims description 10
• VEFDQCSIVBIYFQ-UHFFFAOYSA-N 4-phenylquinazoline Chemical compound C1=CC=CC=C1C1=NC=NC2=CC=CC=C12 VEFDQCSIVBIYFQ-UHFFFAOYSA-N 0.000 claims description 9
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 9
• 125000005059 halophenyl group Chemical group 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 108090000623 proteins and genes Proteins 0.000 claims description 9
• 125000002431 aminoalkoxy group Chemical group 0.000 claims description 8
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000000623 heterocyclic group Chemical group 0.000 claims description 7
• 125000006524 alkoxy alkyl amino group Chemical group 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000003367 polycyclic group Chemical group 0.000 claims description 6
• 102000004169 proteins and genes Human genes 0.000 claims description 6
• 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 6
• 206010004146 Basal cell carcinoma Diseases 0.000 claims description 5
• 201000009030 Carcinoma Diseases 0.000 claims description 5
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
• 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
• 201000004101 esophageal cancer Diseases 0.000 claims description 5
• 150000002430 hydrocarbons Chemical group 0.000 claims description 5
• 206010027191 meningioma Diseases 0.000 claims description 5
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• LOCUXGFHUYBUHF-UHFFFAOYSA-N 4-phenylquinoline Chemical compound C1=CC=CC=C1C1=CC=NC2=CC=CC=C12 LOCUXGFHUYBUHF-UHFFFAOYSA-N 0.000 claims description 4
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 4
• 208000034578 Multiple myelomas Diseases 0.000 claims description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
• FSEXLNMNADBYJU-UHFFFAOYSA-N alpha-Phenylquinoline Natural products C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=N1 FSEXLNMNADBYJU-UHFFFAOYSA-N 0.000 claims description 4
• 201000000053 blastoma Diseases 0.000 claims description 4
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000005265 dialkylamine group Chemical group 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 201000008184 embryoma Diseases 0.000 claims description 4
• 206010017758 gastric cancer Diseases 0.000 claims description 4
• 201000001441 melanoma Diseases 0.000 claims description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Natural products O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
• 201000011549 stomach cancer Diseases 0.000 claims description 4
• 125000006168 tricyclic group Chemical group 0.000 claims description 4
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
• 206010009944 Colon cancer Diseases 0.000 claims description 3
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
• 206010060862 Prostate cancer Diseases 0.000 claims description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
• 208000029742 colonic neoplasm Diseases 0.000 claims description 3
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
• 208000005017 glioblastoma Diseases 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 230000001404 mediated effect Effects 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 229960005181 morphine Drugs 0.000 claims description 3
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• ZAFOSXDWAXJBFW-UHFFFAOYSA-N 4-[(4-phenylquinazolin-2-yl)amino]-n-(1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide Chemical compound C=1C=C2CCNCC2=CC=1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 ZAFOSXDWAXJBFW-UHFFFAOYSA-N 0.000 claims description 2
• 206010036790 Productive cough Diseases 0.000 claims description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
• KQHQHMLMEPXFCR-UHFFFAOYSA-N n-[2-(2-hydroxyethyl)-3,4-dihydro-1h-isoquinolin-5-yl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1N(CCO)CCC2=C1C=CC=C2NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 KQHQHMLMEPXFCR-UHFFFAOYSA-N 0.000 claims description 2
• OTFKGCFEAKXVFD-UHFFFAOYSA-N n-[2-(2-phenylmethoxyethyl)-3,4-dihydro-1h-isoquinolin-5-yl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1C(=O)NC(C=1CC2)=CC=CC=1CN2CCOCC1=CC=CC=C1 OTFKGCFEAKXVFD-UHFFFAOYSA-N 0.000 claims description 2
• URQYKPOCUMNXHE-UHFFFAOYSA-N n-[2-methyl-4-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=1CN1CCOCC1 URQYKPOCUMNXHE-UHFFFAOYSA-N 0.000 claims description 2
• NYNBCLKVLOSIHL-UHFFFAOYSA-N n-[2-methyl-5-[(4-methylpentan-2-ylamino)methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)CC(C)NCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 NYNBCLKVLOSIHL-UHFFFAOYSA-N 0.000 claims description 2
• DRPTXLNWDABLMT-UHFFFAOYSA-N n-[2-methyl-5-[[methyl(propan-2-yl)amino]methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)N(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DRPTXLNWDABLMT-UHFFFAOYSA-N 0.000 claims description 2
• OSNIBHGOBXLOPI-UHFFFAOYSA-N n-[3-[(dimethylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CN(C)CC1=CC=CC(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1C OSNIBHGOBXLOPI-UHFFFAOYSA-N 0.000 claims description 2
• DJACOSKMIKIWCU-UHFFFAOYSA-N n-[4-[(dimethylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(CN(C)C)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 DJACOSKMIKIWCU-UHFFFAOYSA-N 0.000 claims description 2
• MDAIZJWABQGGRX-UHFFFAOYSA-N n-[4-[[ethyl(2-hydroxyethyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(CN(CCO)CC)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 MDAIZJWABQGGRX-UHFFFAOYSA-N 0.000 claims description 2
• FEXORTYBOBXEOL-UHFFFAOYSA-N n-[5-(3,4-dihydro-1h-isoquinolin-2-ylmethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CN2CC3=CC=CC=C3CC2)C=C1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 FEXORTYBOBXEOL-UHFFFAOYSA-N 0.000 claims description 2
• ASMNILRGTXPIGR-UHFFFAOYSA-N n-[5-(diethylaminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCN(CC)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 ASMNILRGTXPIGR-UHFFFAOYSA-N 0.000 claims description 2
• BWBIVHMGPPJRJN-UHFFFAOYSA-N n-[5-[(2,6-dimethylpiperidin-1-yl)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1CCCC(C)N1CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 BWBIVHMGPPJRJN-UHFFFAOYSA-N 0.000 claims description 2
• ZVVYPBJOOCOJIT-UHFFFAOYSA-N n-[5-[(tert-butylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CNC(C)(C)C)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 ZVVYPBJOOCOJIT-UHFFFAOYSA-N 0.000 claims description 2
• WGNREIBKBUTPQV-UHFFFAOYSA-N n-[5-[[2-hydroxyethyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound OCCN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 WGNREIBKBUTPQV-UHFFFAOYSA-N 0.000 claims description 2
• DARJFFTXAKAKSI-UHFFFAOYSA-N n-[5-[[di(propan-2-yl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)N(C(C)C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DARJFFTXAKAKSI-UHFFFAOYSA-N 0.000 claims description 2
• JVPVVOREIIPMFY-UHFFFAOYSA-N n-[5-[[ethyl(2-hydroxyethyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound OCCN(CC)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 JVPVVOREIIPMFY-UHFFFAOYSA-N 0.000 claims description 2
• JSPWWAOAPVYARG-UHFFFAOYSA-N n-[5-[[ethyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 JSPWWAOAPVYARG-UHFFFAOYSA-N 0.000 claims description 2
• 210000000276 neural tube Anatomy 0.000 claims description 2
• 210000004498 neuroglial cell Anatomy 0.000 claims description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 2
• 201000002528 pancreatic cancer Diseases 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 230000002062 proliferating effect Effects 0.000 claims description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
• 208000024794 sputum Diseases 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 14
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 8
• 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 claims 5
• QRGQGYNVGTXUJG-UHFFFAOYSA-N 4-[[4-(4-chlorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC(Cl)=CC=4)N=3)=CC=2)=C1 QRGQGYNVGTXUJG-UHFFFAOYSA-N 0.000 claims 3
• GZVHEAJQGPRDLQ-UHFFFAOYSA-N 6-phenyl-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(C=2C=CC=CC=2)=N1 GZVHEAJQGPRDLQ-UHFFFAOYSA-N 0.000 claims 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
• 125000006317 cyclopropyl amino group Chemical group 0.000 claims 2
• NDJKXXJCMXVBJW-UHFFFAOYSA-N heptadecane Chemical compound CCCCCCCCCCCCCCCCC NDJKXXJCMXVBJW-UHFFFAOYSA-N 0.000 claims 2
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
• JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 claims 1
• SUFSWPVZJJKPPB-UHFFFAOYSA-N 3-fluoro-n-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=C(F)C(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CN1CCOCC1 SUFSWPVZJJKPPB-UHFFFAOYSA-N 0.000 claims 1
• 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
• JLVCFVJZEJNRPZ-UHFFFAOYSA-N 4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 JLVCFVJZEJNRPZ-UHFFFAOYSA-N 0.000 claims 1
• OKJVSPHBGBUOFH-UHFFFAOYSA-N 4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-n-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC(Cl)=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CN1CCOCC1 OKJVSPHBGBUOFH-UHFFFAOYSA-N 0.000 claims 1
• QZZAWWIOPKODSR-UHFFFAOYSA-N 4-[(6-chloro-4-phenylquinazolin-2-yl)amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC(Cl)=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 QZZAWWIOPKODSR-UHFFFAOYSA-N 0.000 claims 1
• LIVWRSLWMPOFSZ-UHFFFAOYSA-N 4-[[4-(2,3-dichlorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C(=C(Cl)C=CC=4)Cl)N=3)=CC=2)=C1 LIVWRSLWMPOFSZ-UHFFFAOYSA-N 0.000 claims 1
• IMXPOXAFXXFFPH-UHFFFAOYSA-N 4-[[4-(2,4-difluorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C(=CC(F)=CC=4)F)N=3)=CC=2)=C1 IMXPOXAFXXFFPH-UHFFFAOYSA-N 0.000 claims 1
• ROZSOIKMONYZMZ-UHFFFAOYSA-N 4-[[4-(2-chlorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C(=CC=CC=4)Cl)N=3)=CC=2)=C1 ROZSOIKMONYZMZ-UHFFFAOYSA-N 0.000 claims 1
• BERKIVZHBBLWKK-UHFFFAOYSA-N 4-[[4-(3,4-dichlorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=C(Cl)C(Cl)=CC=4)N=3)=CC=2)=C1 BERKIVZHBBLWKK-UHFFFAOYSA-N 0.000 claims 1
• SCCOJJAPLYZION-UHFFFAOYSA-N 4-[[4-(3,5-dichlorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=C(Cl)C=C(Cl)C=4)N=3)=CC=2)=C1 SCCOJJAPLYZION-UHFFFAOYSA-N 0.000 claims 1
• XYXBZADWVBHTTJ-UHFFFAOYSA-N 4-[[4-(3,5-difluorophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=C(F)C=C(F)C=4)N=3)=CC=2)=C1 XYXBZADWVBHTTJ-UHFFFAOYSA-N 0.000 claims 1
• XDGGFASCQSRGRY-UHFFFAOYSA-N 4-[[4-(3-bromophenyl)quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=C(Br)C=CC=4)N=3)=CC=2)=C1 XDGGFASCQSRGRY-UHFFFAOYSA-N 0.000 claims 1
• LAZWQSPJOCPSMR-UHFFFAOYSA-N 4-[[4-[2-(2-bromophenyl)phenyl]quinazolin-2-yl]amino]-n-[5-[(dimethylamino)methyl]-2-methylphenyl]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C(=CC=CC=4)C=4C(=CC=CC=4)Br)N=3)=CC=2)=C1 LAZWQSPJOCPSMR-UHFFFAOYSA-N 0.000 claims 1
• NOHMANQKYARVCY-UHFFFAOYSA-N 4-cyclopropylquinazoline Chemical compound C1CC1C1=NC=NC2=CC=CC=C12 NOHMANQKYARVCY-UHFFFAOYSA-N 0.000 claims 1
• IUQMWGWDJZHCOD-UHFFFAOYSA-N 4-ethylquinazoline Chemical compound C1=CC=C2C(CC)=NC=NC2=C1 IUQMWGWDJZHCOD-UHFFFAOYSA-N 0.000 claims 1
• 241000156724 Antirhea Species 0.000 claims 1
• 206010033128 Ovarian cancer Diseases 0.000 claims 1
• 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
• 208000024313 Testicular Neoplasms Diseases 0.000 claims 1
• 206010057644 Testis cancer Diseases 0.000 claims 1
• 201000009036 biliary tract cancer Diseases 0.000 claims 1
• 208000020790 biliary tract neoplasm Diseases 0.000 claims 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
• 125000005343 heterocyclic alkyl group Chemical group 0.000 claims 1
• NIKJMHMVJKTMLN-UHFFFAOYSA-N n-(2-methyl-3,4-dihydro-1h-isoquinolin-7-yl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C2CN(C)CCC2=CC=C1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 NIKJMHMVJKTMLN-UHFFFAOYSA-N 0.000 claims 1
• FFVUFBVIFKQIEQ-UHFFFAOYSA-N n-[2-methyl-3-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=CC=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=C1CN1CCOCC1 FFVUFBVIFKQIEQ-UHFFFAOYSA-N 0.000 claims 1
• YTYIXENBFITJDP-UHFFFAOYSA-N n-[2-methyl-5-(1-morpholin-4-ylethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=CC=1C(C)N1CCOCC1 YTYIXENBFITJDP-UHFFFAOYSA-N 0.000 claims 1
• LDRCXCKPEAILRT-UHFFFAOYSA-N n-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-methylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C)N=3)=CC=2)C(C)=CC=C1CN1CCOCC1 LDRCXCKPEAILRT-UHFFFAOYSA-N 0.000 claims 1
• VWVNEVNBFBKBAS-UHFFFAOYSA-N n-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-morpholin-4-ylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(N4CCOCC4)N=3)=CC=2)C(C)=CC=C1CN1CCOCC1 VWVNEVNBFBKBAS-UHFFFAOYSA-N 0.000 claims 1
• SNQWXWNQJJRRDI-UHFFFAOYSA-N n-[2-methyl-5-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CN1CCOCC1 SNQWXWNQJJRRDI-UHFFFAOYSA-N 0.000 claims 1
• XJOPTFLHWRUCHN-UHFFFAOYSA-N n-[2-methyl-5-[(2-methylpropylamino)methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)CNCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 XJOPTFLHWRUCHN-UHFFFAOYSA-N 0.000 claims 1
• DPXYLKSVGQNVIT-UHFFFAOYSA-N n-[2-methyl-5-[(propan-2-ylamino)methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)NCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DPXYLKSVGQNVIT-UHFFFAOYSA-N 0.000 claims 1
• IQOXEKPZSCTWRQ-UHFFFAOYSA-N n-[4-[(2-hydroxyethylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(CNCCO)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 IQOXEKPZSCTWRQ-UHFFFAOYSA-N 0.000 claims 1
• NDTZJYIHPHSDPN-UHFFFAOYSA-N n-[5-(3,4-dihydro-2h-quinolin-1-ylmethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CN2C3=CC=CC=C3CCC2)C=C1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 NDTZJYIHPHSDPN-UHFFFAOYSA-N 0.000 claims 1
• HVJFQMGMRNOCKR-UHFFFAOYSA-N n-[5-(aminomethyl)-2-methylphenyl]-4-[[4-(4-chlorophenyl)quinazolin-2-yl]amino]benzamide Chemical compound CC1=CC=C(CN)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC(Cl)=CC=2)=C(C=CC=C2)C2=N1 HVJFQMGMRNOCKR-UHFFFAOYSA-N 0.000 claims 1
• GQHHTMCZAVVPSD-UHFFFAOYSA-N n-[5-[(1,3-dihydroxypropan-2-ylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CNC(CO)CO)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 GQHHTMCZAVVPSD-UHFFFAOYSA-N 0.000 claims 1
• OJWWTCDBAORAGZ-UHFFFAOYSA-N n-[5-[(butan-2-ylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCC(C)NCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 OJWWTCDBAORAGZ-UHFFFAOYSA-N 0.000 claims 1
• MUUQQJCYXFFKIJ-UHFFFAOYSA-N n-[5-[(cyclopentylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CNC1CCCC1 MUUQQJCYXFFKIJ-UHFFFAOYSA-N 0.000 claims 1
• UCNRPSPLERZSQR-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[(4-propan-2-ylquinazolin-2-yl)amino]benzamide Chemical compound N=1C2=CC=CC=C2C(C(C)C)=NC=1NC(C=C1)=CC=C1C(=O)NC1=CC(CN(C)C)=CC=C1C UCNRPSPLERZSQR-UHFFFAOYSA-N 0.000 claims 1
• JYTNEEABXBCAJC-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[(4-thiophen-2-ylquinazolin-2-yl)amino]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4SC=CC=4)N=3)=CC=2)=C1 JYTNEEABXBCAJC-UHFFFAOYSA-N 0.000 claims 1
• FFNGTCFUIXIMOM-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[[4-(1-methylpyrrol-2-yl)quinazolin-2-yl]amino]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4N(C=CC=4)C)N=3)=CC=2)=C1 FFNGTCFUIXIMOM-UHFFFAOYSA-N 0.000 claims 1
• PGUCCZFJGXTXNS-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[[4-(2-fluorophenyl)quinazolin-2-yl]amino]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C(=CC=CC=4)F)N=3)=CC=2)=C1 PGUCCZFJGXTXNS-UHFFFAOYSA-N 0.000 claims 1
• FHHOSLXXKWGBTO-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[[4-(4-fluorophenyl)quinazolin-2-yl]amino]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC(F)=CC=4)N=3)=CC=2)=C1 FHHOSLXXKWGBTO-UHFFFAOYSA-N 0.000 claims 1
• RWVKLLAQUGFTJT-UHFFFAOYSA-N n-[5-[1-(dimethylamino)ethyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CN(C)C(C)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 RWVKLLAQUGFTJT-UHFFFAOYSA-N 0.000 claims 1
• DFPYAQAEAOTHOA-UHFFFAOYSA-N n-[5-[1-[bis(3,3,3-trifluoropropyl)amino]ethyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound FC(F)(F)CCN(CCC(F)(F)F)C(C)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DFPYAQAEAOTHOA-UHFFFAOYSA-N 0.000 claims 1
• KSCCVKRYPABLMZ-UHFFFAOYSA-N n-[5-[1-[ethyl(3,3,3-trifluoropropyl)amino]ethyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound FC(F)(F)CCN(CC)C(C)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 KSCCVKRYPABLMZ-UHFFFAOYSA-N 0.000 claims 1
• FNTFWBIALPRAEY-UHFFFAOYSA-N n-[5-[[benzyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-ethylquinazolin-2-yl)amino]benzamide Chemical compound N=1C2=CC=CC=C2C(CC)=NC=1NC(C=C1)=CC=C1C(=O)NC(C(=CC=1)C)=CC=1CN(C)CC1=CC=CC=C1 FNTFWBIALPRAEY-UHFFFAOYSA-N 0.000 claims 1
• ASMNKAVXAIEYHP-UHFFFAOYSA-N n-[5-[[benzyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=CC=1CN(C)CC1=CC=CC=C1 ASMNKAVXAIEYHP-UHFFFAOYSA-N 0.000 claims 1
• CULKOPOEQXFXAF-UHFFFAOYSA-N n-[5-[[benzyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-propan-2-ylquinazolin-2-yl)amino]benzamide Chemical compound N=1C2=CC=CC=C2C(C(C)C)=NC=1NC(C=C1)=CC=C1C(=O)NC(C(=CC=1)C)=CC=1CN(C)CC1=CC=CC=C1 CULKOPOEQXFXAF-UHFFFAOYSA-N 0.000 claims 1
• WZEBOLAOPXUTHP-UHFFFAOYSA-N n-[5-[[cyclohexyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1CCCCC1N(C)CC(C=1)=CC=C(C)C=1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 WZEBOLAOPXUTHP-UHFFFAOYSA-N 0.000 claims 1
• WJHPFXZFNBJBGS-UHFFFAOYSA-N n-[5-[[cyclopropyl(methyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1CC1N(C)CC(C=1)=CC=C(C)C=1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 WJHPFXZFNBJBGS-UHFFFAOYSA-N 0.000 claims 1
• KNSBQCJOONDBEV-UHFFFAOYSA-N n-[5-[[ethyl(2,2,2-trifluoroethyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound FC(F)(F)CN(CC)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 KNSBQCJOONDBEV-UHFFFAOYSA-N 0.000 claims 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
• 125000006308 propyl amino group Chemical group 0.000 claims 1
• 210000003802 sputum Anatomy 0.000 claims 1
• 201000003120 testicular cancer Diseases 0.000 claims 1
• 238000005481 NMR spectroscopy Methods 0.000 description 116
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 111
• 239000000543 intermediate Substances 0.000 description 110
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 90
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
• 239000002585 base Substances 0.000 description 58
• 239000002904 solvent Substances 0.000 description 52
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 239000000243 solution Substances 0.000 description 29
• 125000004076 pyridyl group Chemical group 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
• 239000007787 solid Substances 0.000 description 27
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 150000003254 radicals Chemical class 0.000 description 19
• 125000003342 alkenyl group Chemical group 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
• 125000004475 heteroaralkyl group Chemical group 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• 235000019439 ethyl acetate Nutrition 0.000 description 13
• 239000000047 product Substances 0.000 description 13
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 229940002612 prodrug Drugs 0.000 description 11
• 239000000651 prodrug Substances 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
• 239000007821 HATU Substances 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• 208000009956 adenocarcinoma Diseases 0.000 description 10
• 125000000304 alkynyl group Chemical group 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 239000008194 pharmaceutical composition Substances 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 9
• 206010039491 Sarcoma Diseases 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 208000011580 syndromic disease Diseases 0.000 description 9
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 125000003710 aryl alkyl group Chemical group 0.000 description 8
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 8
• 125000003226 pyrazolyl group Chemical group 0.000 description 8
• 238000005160 1H NMR spectroscopy Methods 0.000 description 7
• 206010025323 Lymphomas Diseases 0.000 description 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
• 125000003302 alkenyloxy group Chemical group 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000012320 chlorinating reagent Substances 0.000 description 7
• 125000001309 chloro group Chemical group Cl* 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 125000002541 furyl group Chemical group 0.000 description 7
• 150000004677 hydrates Chemical class 0.000 description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• IQQYKULLKVYXCS-UHFFFAOYSA-N n-benzyldecan-1-amine Chemical compound CCCCCCCCCCNCC1=CC=CC=C1 IQQYKULLKVYXCS-UHFFFAOYSA-N 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 125000000168 pyrrolyl group Chemical group 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 125000001544 thienyl group Chemical group 0.000 description 7
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 6
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
• 150000001204 N-oxides Chemical class 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
• 125000001153 fluoro group Chemical group F* 0.000 description 6
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 6
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 6
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
• 230000002503 metabolic effect Effects 0.000 description 6
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 6
• 229960004889 salicylic acid Drugs 0.000 description 6
• 239000012258 stirred mixture Substances 0.000 description 6
• 125000000547 substituted alkyl group Chemical group 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
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• 206010001233 Adenoma benign Diseases 0.000 description 5
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
• 125000003943 azolyl group Chemical group 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 5
• 235000015165 citric acid Nutrition 0.000 description 5
• 238000007796 conventional method Methods 0.000 description 5
• 239000007822 coupling agent Substances 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 229910052736 halogen Inorganic materials 0.000 description 5
• 150000002367 halogens Chemical class 0.000 description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 201000010260 leiomyoma Diseases 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 125000002971 oxazolyl group Chemical group 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 125000003107 substituted aryl group Chemical group 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 230000009466 transformation Effects 0.000 description 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• WWZYTCHSHCEEGJ-UHFFFAOYSA-N 4-[(4-phenylquinazolin-2-yl)amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 WWZYTCHSHCEEGJ-UHFFFAOYSA-N 0.000 description 4
• 208000003200 Adenoma Diseases 0.000 description 4
• 239000005711 Benzoic acid Substances 0.000 description 4
• 206010024612 Lipoma Diseases 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 4
• 235000010233 benzoic acid Nutrition 0.000 description 4
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
• 210000000845 cartilage Anatomy 0.000 description 4
• 238000002512 chemotherapy Methods 0.000 description 4
• 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 201000011066 hemangioma Diseases 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000003211 malignant effect Effects 0.000 description 4
• 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 206010041823 squamous cell carcinoma Diseases 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 3
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 3
• SFKMVPQJJGJCMI-UHFFFAOYSA-N 2-chloro-4-phenylquinazoline Chemical compound C=12C=CC=CC2=NC(Cl)=NC=1C1=CC=CC=C1 SFKMVPQJJGJCMI-UHFFFAOYSA-N 0.000 description 3
• 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 3
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
• RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 3
• YYQYARCBWCOUOV-UHFFFAOYSA-N 4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 YYQYARCBWCOUOV-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 3
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• XSRWMYORWAQSNQ-UHFFFAOYSA-N FNCl Chemical compound FNCl XSRWMYORWAQSNQ-UHFFFAOYSA-N 0.000 description 3
• 201000008808 Fibrosarcoma Diseases 0.000 description 3
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 3
• 206010018338 Glioma Diseases 0.000 description 3
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• 229930194542 Keto Natural products 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 3
• XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 3
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
• 108700020796 Oncogene Proteins 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 235000021355 Stearic acid Nutrition 0.000 description 3
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
• 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 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 239000003513 alkali Substances 0.000 description 3
• 125000004702 alkoxy alkyl carbonyl group Chemical group 0.000 description 3
• 125000005083 alkoxyalkoxy group Chemical group 0.000 description 3
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 3
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
• 239000002246 antineoplastic agent Substances 0.000 description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 3
• 229940092714 benzenesulfonic acid Drugs 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 210000000481 breast Anatomy 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 239000004202 carbamide Substances 0.000 description 3
• 235000013985 cinnamic acid Nutrition 0.000 description 3
• 229930016911 cinnamic acid Natural products 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008025 crystallization Effects 0.000 description 3
• 125000004966 cyanoalkyl group Chemical group 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 3
• 229940043264 dodecyl sulfate Drugs 0.000 description 3
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 3
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000001530 fumaric acid Substances 0.000 description 3
• 235000011087 fumaric acid Nutrition 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000000174 gluconic acid Substances 0.000 description 3
• 235000012208 gluconic acid Nutrition 0.000 description 3
• 239000004220 glutamic acid Substances 0.000 description 3
• 235000013922 glutamic acid Nutrition 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 125000000468 ketone group Chemical group 0.000 description 3
• 239000004310 lactic acid Substances 0.000 description 3
• 235000014655 lactic acid 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
• 239000011976 maleic acid Substances 0.000 description 3
• IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 3
• 229960002510 mandelic acid Drugs 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 229940098779 methanesulfonic acid Drugs 0.000 description 3
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 3
• PMILYZUSCUQVEW-UHFFFAOYSA-N n-[5-(hydroxymethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CO)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 PMILYZUSCUQVEW-UHFFFAOYSA-N 0.000 description 3
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 3
• 229910017604 nitric acid Inorganic materials 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• 235000006408 oxalic acid Nutrition 0.000 description 3
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 3
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 3
• 210000000496 pancreas Anatomy 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 3
• 235000019260 propionic acid Nutrition 0.000 description 3
• 210000002307 prostate Anatomy 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 229940107700 pyruvic acid Drugs 0.000 description 3
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 125000003003 spiro group Chemical group 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 229940032147 starch Drugs 0.000 description 3
• 239000008117 stearic acid Substances 0.000 description 3
• 125000005017 substituted alkenyl group Chemical group 0.000 description 3
• 125000004426 substituted alkynyl group Chemical group 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000011975 tartaric acid Substances 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 2
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical group NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-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
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 2
• ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
• UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 2
• FHUBTSLLILWICW-UHFFFAOYSA-N 4-phenyl-1h-quinazolin-2-one Chemical compound C12=CC=CC=C2NC(=O)N=C1C1=CC=CC=C1 FHUBTSLLILWICW-UHFFFAOYSA-N 0.000 description 2
• QJJRVFAVKDCJBV-UHFFFAOYSA-N 4-phenyl-n-piperidin-4-ylquinazolin-2-amine Chemical compound C1CNCCC1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 QJJRVFAVKDCJBV-UHFFFAOYSA-N 0.000 description 2
• IZSHZLKNFQAAKX-UHFFFAOYSA-N 5-cyclopenta-2,4-dien-1-ylcyclopenta-1,3-diene Chemical group C1=CC=CC1C1C=CC=C1 IZSHZLKNFQAAKX-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 206010004593 Bile duct cancer Diseases 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
• 235000001258 Cinchona calisaya Nutrition 0.000 description 2
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 206010058314 Dysplasia Diseases 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 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 2
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• IMAAZOZRMWEDIF-UHFFFAOYSA-N OC1=CC=C(C(C2=CC=CC=C2)C=2C=C(C(=O)O)C=CC2)C=C1 Chemical compound OC1=CC=C(C(C2=CC=CC=C2)C=2C=C(C(=O)O)C=CC2)C=C1 IMAAZOZRMWEDIF-UHFFFAOYSA-N 0.000 description 2
• 108010065129 Patched-1 Receptor Proteins 0.000 description 2
• 102000012850 Patched-1 Receptor Human genes 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 208000031320 Teratogenesis Diseases 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 206010046798 Uterine leiomyoma Diseases 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 125000005090 alkenylcarbonyl group Chemical group 0.000 description 2
• 125000005193 alkenylcarbonyloxy group Chemical group 0.000 description 2
• 125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 2
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 2
• 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 description 2
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 2
• 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 description 2
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 229960001948 caffeine Drugs 0.000 description 2
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 229960001231 choline Drugs 0.000 description 2
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
• YYKJUIOOPHHRFU-UHFFFAOYSA-N cyclohexyl-[4-[(4-phenylquinazolin-2-yl)amino]piperidin-1-yl]methanone Chemical compound C1CC(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)CCN1C(=O)C1CCCCC1 YYKJUIOOPHHRFU-UHFFFAOYSA-N 0.000 description 2
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• 125000005202 dialkylaminocarbonyloxy group Chemical group 0.000 description 2
• 125000004472 dialkylaminosulfonyl group Chemical group 0.000 description 2
• 235000005911 diet Nutrition 0.000 description 2
• 230000037213 diet Effects 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 238000009510 drug design Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 2
• 206010016629 fibroma Diseases 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000009499 grossing Methods 0.000 description 2
• 125000004992 haloalkylamino group Chemical group 0.000 description 2
• 230000003862 health status Effects 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 2
• 125000005113 hydroxyalkoxy group Chemical group 0.000 description 2
• 125000005191 hydroxyalkylamino group Chemical group 0.000 description 2
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• 230000001965 increasing effect Effects 0.000 description 2
• 230000009545 invasion Effects 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 230000004777 loss-of-function mutation Effects 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 230000003020 moisturizing effect Effects 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 210000000066 myeloid cell Anatomy 0.000 description 2
• IQHVMZMNEYKFFM-UHFFFAOYSA-N n-(5-cyano-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(C#N)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 IQHVMZMNEYKFFM-UHFFFAOYSA-N 0.000 description 2
• KLRRGBHZCJLIEL-UHFFFAOYSA-N n-[2-methyl-5-(methylaminomethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CNCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 KLRRGBHZCJLIEL-UHFFFAOYSA-N 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 125000002071 phenylalkoxy group Chemical group 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000002335 preservative effect Effects 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 2
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 2
• 229960000948 quinine Drugs 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 229960001603 tamoxifen Drugs 0.000 description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
• 208000001608 teratocarcinoma Diseases 0.000 description 2
• WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 2
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• DTHKCNXTNNJZSX-UHFFFAOYSA-N (2,6-dichlorophenyl)-[4-[(4-phenylquinazolin-2-yl)amino]piperidin-1-yl]methanone Chemical compound ClC1=CC=CC(Cl)=C1C(=O)N1CCC(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)CC1 DTHKCNXTNNJZSX-UHFFFAOYSA-N 0.000 description 1
• MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
• LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
• BCQKYGYTOHXGLL-UHFFFAOYSA-N (3-amino-4-methylphenyl)methanol Chemical compound CC1=CC=C(CO)C=C1N BCQKYGYTOHXGLL-UHFFFAOYSA-N 0.000 description 1
• HAJKHJOABGFIGP-QMMMGPOBSA-N (8as)-1,2,3,5,6,7,8,8a-octahydroindolizine Chemical compound C1CCCN2CCC[C@@H]21 HAJKHJOABGFIGP-QMMMGPOBSA-N 0.000 description 1
• ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
• VWHSDFNFHGSPLE-UHFFFAOYSA-N 2,3,3a,4,7,7a-hexahydro-1h-indole Chemical compound C1C=CCC2NCCC21 VWHSDFNFHGSPLE-UHFFFAOYSA-N 0.000 description 1
• PHXGAJLBHUUAKB-UHFFFAOYSA-N 2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound O1CCC2OCCC21 PHXGAJLBHUUAKB-UHFFFAOYSA-N 0.000 description 1
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 1
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
• XKFIFYROMAAUDL-UHFFFAOYSA-N 3-amino-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N XKFIFYROMAAUDL-UHFFFAOYSA-N 0.000 description 1
• IEWMNQUBZPVSSV-UHFFFAOYSA-N 3-amino-4-methylbenzonitrile Chemical compound CC1=CC=C(C#N)C=C1N IEWMNQUBZPVSSV-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• IEZXLMDIDXLUDX-UHFFFAOYSA-N 4-[(4-phenylquinazolin-2-yl)amino]-n-(2,3,3-trimethyl-1,4-dihydroisoquinolin-7-yl)benzamide Chemical compound C=1C=C2CC(C)(C)N(C)CC2=CC=1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 IEZXLMDIDXLUDX-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
• OURXRFYZEOUCRM-UHFFFAOYSA-N 4-hydroxymorpholine Chemical group ON1CCOCC1 OURXRFYZEOUCRM-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• LDGSWOVXBURIQE-UHFFFAOYSA-N 4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CC1=CC=C(C(N)=O)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 LDGSWOVXBURIQE-UHFFFAOYSA-N 0.000 description 1
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
• IRXLEBLBUZBKQQ-UHFFFAOYSA-N 7-nitrobicyclo[2.2.1]heptane Chemical compound C1CC2CCC1C2[N+](=O)[O-] IRXLEBLBUZBKQQ-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
• 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 206010007269 Carcinogenicity Diseases 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 208000006332 Choriocarcinoma Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 206010013710 Drug interaction Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 description 1
• 208000007659 Fibroadenoma Diseases 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• 208000021309 Germ cell tumor Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 206010018691 Granuloma Diseases 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
• 206010019629 Hepatic adenoma Diseases 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 241000764238 Isis Species 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• VFPIOXZJOHYRSY-UHFFFAOYSA-N OS(O)=O.Cl.Cl Chemical compound OS(O)=O.Cl.Cl VFPIOXZJOHYRSY-UHFFFAOYSA-N 0.000 description 1
• 244000227633 Ocotea pretiosa Species 0.000 description 1
• 235000004263 Ocotea pretiosa Nutrition 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 208000005678 Rhabdomyoma Diseases 0.000 description 1
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
• 241000239226 Scorpiones Species 0.000 description 1
• 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 235000009754 Vitis X bourquina Nutrition 0.000 description 1
• 235000012333 Vitis X labruscana Nutrition 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 235000014787 Vitis vinifera Nutrition 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 206010048214 Xanthoma Diseases 0.000 description 1
• 206010048215 Xanthomatosis 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
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 150000001299 aldehydes Chemical class 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
• 150000001336 alkenes Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-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
• 150000001408 amides Chemical class 0.000 description 1
• 229960004050 aminobenzoic acid Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 238000007080 aromatic substitution reaction Methods 0.000 description 1
• 125000001691 aryl alkyl amino group Chemical group 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960004365 benzoic acid Drugs 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 201000003149 breast fibroadenoma Diseases 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000001722 carbon compounds Chemical class 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 231100000260 carcinogenicity Toxicity 0.000 description 1
• 230000007670 carcinogenicity Effects 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000003833 cell viability Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 210000003161 choroid Anatomy 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 239000012059 conventional drug carrier Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 1
• UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 208000002445 cystadenocarcinoma Diseases 0.000 description 1
• 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 125000002720 diazolyl group 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
• 125000003963 dichloro group Chemical group Cl* 0.000 description 1
• DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• XOJNEFQLMRCOMS-UHFFFAOYSA-N ditert-butyl(phenyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1 XOJNEFQLMRCOMS-UHFFFAOYSA-N 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 208000014616 embryonal neoplasm Diseases 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 125000002587 enol group Chemical group 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• 229940093499 ethyl acetate Drugs 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
• 229940012017 ethylenediamine Drugs 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 201000010934 exostosis Diseases 0.000 description 1
• 239000003885 eye ointment Substances 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 210000001752 female genitalia Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 238000001030 gas--liquid chromatography Methods 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 229940084910 gliadel Drugs 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 125000004994 halo alkoxy alkyl group Chemical group 0.000 description 1
• 125000000262 haloalkenyl group Chemical group 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 201000002735 hepatocellular adenoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-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
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229960002885 histidine Drugs 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
• 201000001421 hyperglycemia Diseases 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000012739 integrated shape imaging system Methods 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 210000002570 interstitial cell Anatomy 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 208000020082 intraepithelial neoplasia Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 239000007951 isotonicity adjuster Substances 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
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 235000020778 linoleic acid Nutrition 0.000 description 1
• OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940057948 magnesium stearate Drugs 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 201000004593 malignant giant cell tumor Diseases 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 210000002418 meninge Anatomy 0.000 description 1
• 208000010943 meningeal sarcoma Diseases 0.000 description 1
• 201000003776 meninges sarcoma Diseases 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• 229940050176 methyl chloride Drugs 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 229910052750 molybdenum Inorganic materials 0.000 description 1
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 208000009091 myxoma Diseases 0.000 description 1
• QABDLBLINHQPQS-UHFFFAOYSA-N n,n,4-trimethyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CN(C)C(=O)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 QABDLBLINHQPQS-UHFFFAOYSA-N 0.000 description 1
• XWHNPZQTMRSHFX-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 XWHNPZQTMRSHFX-UHFFFAOYSA-N 0.000 description 1
• YQPHOHGZDJWQRK-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CC1=CC=C(C(=O)NCCO)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 YQPHOHGZDJWQRK-UHFFFAOYSA-N 0.000 description 1
• YSLOWGUVSSSJSD-UHFFFAOYSA-N n-(4-methylpyrrolidin-3-yl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1CNCC1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 YSLOWGUVSSSJSD-UHFFFAOYSA-N 0.000 description 1
• YMJXHUCJRHRRBQ-UHFFFAOYSA-N n-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1C(=O)NC(S1)=NN=C1C1CC1 YMJXHUCJRHRRBQ-UHFFFAOYSA-N 0.000 description 1
• PSDMJHWSZKFBJG-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1C(=O)NC(NN=1)=CC=1C1CC1 PSDMJHWSZKFBJG-UHFFFAOYSA-N 0.000 description 1
• YQPHYWFLVNTVLE-UHFFFAOYSA-N n-[1-(1h-benzimidazol-2-yl)piperidin-4-yl]-4-phenylquinazolin-2-amine Chemical compound C1CN(C=2NC3=CC=CC=C3N=2)CCC1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 YQPHYWFLVNTVLE-UHFFFAOYSA-N 0.000 description 1
• WWOIJOPBCXWYJE-UHFFFAOYSA-N n-[2,5-bis(hydroxymethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound OCC1=CC=C(CO)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 WWOIJOPBCXWYJE-UHFFFAOYSA-N 0.000 description 1
• IFIDXPPWBVVFMA-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 IFIDXPPWBVVFMA-UHFFFAOYSA-N 0.000 description 1
• PEOVIIGPGKJNRJ-UHFFFAOYSA-N n-[2-methyl-5-(piperidin-1-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CN1CCCCC1 PEOVIIGPGKJNRJ-UHFFFAOYSA-N 0.000 description 1
• DSFZWIMNYDFWFW-UHFFFAOYSA-N n-[2-methyl-5-(propylaminomethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCCNCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DSFZWIMNYDFWFW-UHFFFAOYSA-N 0.000 description 1
• AONGBJCHPPIXGI-UHFFFAOYSA-N n-[2-methyl-5-(pyrrolidin-1-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CN1CCCC1 AONGBJCHPPIXGI-UHFFFAOYSA-N 0.000 description 1
• SKVLCMYLZMPQTA-UHFFFAOYSA-N n-[2-methyl-5-[(3-methylbutan-2-ylamino)methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC(C)C(C)NCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 SKVLCMYLZMPQTA-UHFFFAOYSA-N 0.000 description 1
• FWWJAUAWSDJQBU-PPOKSSTKSA-N n-[2-methyl-5-[(e)-morpholin-4-yliminomethyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1\C=N\N1CCOCC1 FWWJAUAWSDJQBU-PPOKSSTKSA-N 0.000 description 1
• XYMWWSHDNQBJKA-UHFFFAOYSA-N n-[3-(diethylaminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCN(CC)CC1=CC=CC(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1C XYMWWSHDNQBJKA-UHFFFAOYSA-N 0.000 description 1
• DKQDLAQOFYVYSX-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]-4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CN(C)CCCNC(=O)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 DKQDLAQOFYVYSX-UHFFFAOYSA-N 0.000 description 1
• WWYGEUICRXRWNI-UHFFFAOYSA-N n-[3-(morpholin-4-ylmethyl)phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C=1C=C(NC=2N=C3C=CC=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1C(=O)NC(C=1)=CC=CC=1CN1CCOCC1 WWYGEUICRXRWNI-UHFFFAOYSA-N 0.000 description 1
• NNUMAPVWRCYJDV-UHFFFAOYSA-N n-[3-[(dimethylamino)methyl]phenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CN(C)CC1=CC=CC(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 NNUMAPVWRCYJDV-UHFFFAOYSA-N 0.000 description 1
• JPVGACJNIDCWJA-UHFFFAOYSA-N n-[4-(diethylaminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(CN(CC)CC)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 JPVGACJNIDCWJA-UHFFFAOYSA-N 0.000 description 1
• CHMROFQVUGLEGU-UHFFFAOYSA-N n-[4-[[ethyl(propan-2-yl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(CN(CC)C(C)C)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 CHMROFQVUGLEGU-UHFFFAOYSA-N 0.000 description 1
• ARHBPFMQADPXDZ-UHFFFAOYSA-N n-[5-(2,5-diazabicyclo[2.2.1]heptane-2-carbonyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(C(=O)N2C3CC(NC3)C2)C=C1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 ARHBPFMQADPXDZ-UHFFFAOYSA-N 0.000 description 1
• SFUWLBMEXWGHBK-UHFFFAOYSA-N n-[5-(7-azabicyclo[2.2.1]heptan-7-ylmethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CN2C3CCC2CC3)C=C1NC(=O)C(C=C1)=CC=C1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 SFUWLBMEXWGHBK-UHFFFAOYSA-N 0.000 description 1
• USQWXDFTGIUMMS-UHFFFAOYSA-N n-[5-(aminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CN)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 USQWXDFTGIUMMS-UHFFFAOYSA-N 0.000 description 1
• FXGZKSPJWFOLTD-UHFFFAOYSA-N n-[5-(chloromethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC=C(CCl)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 FXGZKSPJWFOLTD-UHFFFAOYSA-N 0.000 description 1
• QULPVEKQAQFBGQ-UHFFFAOYSA-N n-[5-(ethylaminomethyl)-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCNCC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 QULPVEKQAQFBGQ-UHFFFAOYSA-N 0.000 description 1
• WLVYWYLHJVTAIL-UHFFFAOYSA-N n-[5-[(cyclopropylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound C1=C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)C(C)=CC=C1CNC1CC1 WLVYWYLHJVTAIL-UHFFFAOYSA-N 0.000 description 1
• MXCYPBOMBCPTNK-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CN(C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 MXCYPBOMBCPTNK-UHFFFAOYSA-N 0.000 description 1
• WFRBPRJVTIBEQO-UHFFFAOYSA-N n-[5-[[bis(2-methoxyethyl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound COCCN(CCOC)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 WFRBPRJVTIBEQO-UHFFFAOYSA-N 0.000 description 1
• ODSBCFCOFPWUKD-UHFFFAOYSA-N n-[5-[[ethyl(propan-2-yl)amino]methyl]-2-methylphenyl]-4-[(4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CCN(C(C)C)CC1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 ODSBCFCOFPWUKD-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• LRQWKRSDCMNBOS-UHFFFAOYSA-N n-hydroxy-4-methyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CC1=CC=C(C(=O)NO)C=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=CC=C2)C2=N1 LRQWKRSDCMNBOS-UHFFFAOYSA-N 0.000 description 1
• RBLOJETWIAVFPB-UHFFFAOYSA-N n-methoxy-n,4-dimethyl-3-[[4-[(4-phenylquinazolin-2-yl)amino]benzoyl]amino]benzamide Chemical compound CON(C)C(=O)C1=CC=C(C)C(NC(=O)C=2C=CC(NC=3N=C4C=CC=CC4=C(C=4C=CC=CC=4)N=3)=CC=2)=C1 RBLOJETWIAVFPB-UHFFFAOYSA-N 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 201000004662 neurofibroma of spinal cord Diseases 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 208000003388 osteoid osteoma Diseases 0.000 description 1
• 208000008798 osteoma Diseases 0.000 description 1
• 229940127084 other anti-cancer agent Drugs 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• JETGRRZTECZVLO-UHFFFAOYSA-N phenyl-[4-[(4-phenylquinazolin-2-yl)amino]piperidin-1-yl]methanone Chemical compound C=1C=CC=CC=1C(=O)N(CC1)CCC1NC(N=C1C=CC=CC1=1)=NC=1C1=CC=CC=C1 JETGRRZTECZVLO-UHFFFAOYSA-N 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• 229940075999 phytosterol ester Drugs 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 150000004032 porphyrins Chemical group 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
• 230000001855 preneoplastic effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 229960004063 propylene glycol Drugs 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 229910052707 ruthenium Inorganic materials 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000000967 suction filtration Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229920001864 tannin Polymers 0.000 description 1
• 239000001648 tannin Substances 0.000 description 1
• 235000018553 tannin Nutrition 0.000 description 1
• 229960004964 temozolomide Drugs 0.000 description 1
• LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
• 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
• 230000002381 testicular Effects 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229940117013 triethanolamine oleate Drugs 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 208000022271 tubular adenoma Diseases 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1