BG105842A - Заместени бициклени производни, полезни като противоракови средства - Google Patents
Заместени бициклени производни, полезни като противоракови средства Download PDFInfo
- Publication number
- BG105842A BG105842A BG105842A BG10584201A BG105842A BG 105842 A BG105842 A BG 105842A BG 105842 A BG105842 A BG 105842A BG 10584201 A BG10584201 A BG 10584201A BG 105842 A BG105842 A BG 105842A
- Authority
- BG
- Bulgaria
- Prior art keywords
- quinazolin
- methyl
- phenoxy
- piperidin
- phenylamino
- Prior art date
Links
- 125000002619 bicyclic group Chemical group 0.000 title claims description 7
- 239000002246 antineoplastic agent Substances 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 238000000034 method Methods 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 239000012453 solvate Substances 0.000 claims abstract description 17
- 241000124008 Mammalia Species 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 320
- 206010028980 Neoplasm Diseases 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 230000011712 cell development Effects 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 201000011510 cancer Diseases 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 239000003112 inhibitor Substances 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- JSLQGYQJIYKIPZ-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2CCC1(O)CCCNC1 JSLQGYQJIYKIPZ-UHFFFAOYSA-N 0.000 claims description 7
- YIIINVCRRYAISL-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 YIIINVCRRYAISL-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 6
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 230000000340 anti-metabolite Effects 0.000 claims description 5
- 229940100197 antimetabolite Drugs 0.000 claims description 5
- 239000002256 antimetabolite Substances 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 229940088598 enzyme Drugs 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 239000003102 growth factor Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000002280 anti-androgenic effect Effects 0.000 claims description 4
- 230000003388 anti-hormonal effect Effects 0.000 claims description 4
- 239000000051 antiandrogen Substances 0.000 claims description 4
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 239000012444 intercalating antibiotic Substances 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 230000000394 mitotic effect Effects 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 206010038038 rectal cancer Diseases 0.000 claims description 4
- 201000001275 rectum cancer Diseases 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- VFKIMJALKPOEOX-UHFFFAOYSA-N 3-[2-[4-(3-bromo-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(Br)C(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCCNC1 VFKIMJALKPOEOX-UHFFFAOYSA-N 0.000 claims description 3
- ADMHWFAEBKYSHU-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(F)=CC=3)C2=CC=1C#CC1(O)CCCNC1 ADMHWFAEBKYSHU-UHFFFAOYSA-N 0.000 claims description 3
- HOIDGDXRYIGDKF-UHFFFAOYSA-N 3-[2-[4-(3-ethynylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(C=CC=3)C#C)C2=CC=1C#CC1(O)CCCNC1 HOIDGDXRYIGDKF-UHFFFAOYSA-N 0.000 claims description 3
- YRBKPOAMQPIYEW-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-7-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=CC=2)=NC=NC1=CC=2C#CC1(O)CCCNC1 YRBKPOAMQPIYEW-UHFFFAOYSA-N 0.000 claims description 3
- QJOPITIHJWIVBW-UHFFFAOYSA-N 3-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCCNC1 QJOPITIHJWIVBW-UHFFFAOYSA-N 0.000 claims description 3
- HKFWUFNATZHTKI-UHFFFAOYSA-N 3-[2-[4-[(5-methyl-6-phenoxypyridin-3-yl)amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1N=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 HKFWUFNATZHTKI-UHFFFAOYSA-N 0.000 claims description 3
- WUSUIGDZTDZFKP-UHFFFAOYSA-N 3-[2-[4-[4-(benzenesulfonyl)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(S(=O)(=O)C=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 WUSUIGDZTDZFKP-UHFFFAOYSA-N 0.000 claims description 3
- WKBYAFBZDBPUPF-UHFFFAOYSA-N 4-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCOCC1 WKBYAFBZDBPUPF-UHFFFAOYSA-N 0.000 claims description 3
- ZMZQPHTZYNIRJX-UHFFFAOYSA-N 4-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCNCC1 ZMZQPHTZYNIRJX-UHFFFAOYSA-N 0.000 claims description 3
- RMNQYVDQAUPXRX-UHFFFAOYSA-N 4-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]-n-methylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCN1CC#CC1=CC=C(N=CN=C2NC=3C=C(OC)C(OC=4C=CC=CC=4)=CC=3)C2=C1 RMNQYVDQAUPXRX-UHFFFAOYSA-N 0.000 claims description 3
- DUPCNZPIRGSKIS-UHFFFAOYSA-N 6-[2-(4-aminooxan-4-yl)ethynyl]-n-[1-(benzenesulfonyl)indol-5-yl]quinazolin-4-amine Chemical compound C=1C=C2N=CN=C(NC=3C=C4C=CN(C4=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=CC=1C#CC1(N)CCOCC1 DUPCNZPIRGSKIS-UHFFFAOYSA-N 0.000 claims description 3
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- 206010061424 Anal cancer Diseases 0.000 claims description 3
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 3
- 206010005949 Bone cancer Diseases 0.000 claims description 3
- 208000018084 Bone neoplasm Diseases 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 208000017604 Hodgkin disease Diseases 0.000 claims description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 3
- 206010061252 Intraocular melanoma Diseases 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 3
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 206010046458 Urethral neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- 201000005969 Uveal melanoma Diseases 0.000 claims description 3
- 201000011165 anus cancer Diseases 0.000 claims description 3
- 208000025997 central nervous system neoplasm Diseases 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 231100000433 cytotoxic Toxicity 0.000 claims description 3
- 230000001472 cytotoxic effect Effects 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 208000026037 malignant tumor of neck Diseases 0.000 claims description 3
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- BOOACOKUUQHXOX-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCNC1 BOOACOKUUQHXOX-UHFFFAOYSA-N 0.000 claims description 3
- ZMLQORCDQBDHCT-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-(2-piperidin-4-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCNCC1 ZMLQORCDQBDHCT-UHFFFAOYSA-N 0.000 claims description 3
- DHXJSZZGLLJFCL-UHFFFAOYSA-N n-[1-(benzenesulfonyl)indol-5-yl]-6-(2-piperidin-4-ylethynyl)quinazolin-4-amine Chemical compound C1=CC2=CC(NC=3C4=CC(=CC=C4N=CN=3)C#CC3CCNCC3)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 DHXJSZZGLLJFCL-UHFFFAOYSA-N 0.000 claims description 3
- CTUVADQGSIBWHM-UHFFFAOYSA-N n-[3-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]acetamide Chemical compound C12=CC(C#CCNC(=O)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 CTUVADQGSIBWHM-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 201000002575 ocular melanoma Diseases 0.000 claims description 3
- 230000000849 parathyroid Effects 0.000 claims description 3
- 208000016800 primary central nervous system lymphoma Diseases 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 201000010132 spinal cord glioma Diseases 0.000 claims description 3
- 208000037959 spinal tumor Diseases 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- LCSKDSPTQOLVAF-QFIPXVFZSA-N (3s)-3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-n-methylpiperidine-1-carboxamide Chemical compound C1N(C(=O)NC)CCC[C@H]1C#CC1=CC=C(N=CN=C2NC=3C=C(OC)C(OC=4C=CC=CC=4)=CC=3)C2=C1 LCSKDSPTQOLVAF-QFIPXVFZSA-N 0.000 claims description 2
- RCKFOMMDLQFOKY-QHCPKHFHSA-N (3s)-n-methyl-3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidine-1-carboxamide Chemical compound C1N(C(=O)NC)CCC[C@H]1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 RCKFOMMDLQFOKY-QHCPKHFHSA-N 0.000 claims description 2
- KGPYXNKNYVFNEW-UHFFFAOYSA-N 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-4-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCC(O)CC1 KGPYXNKNYVFNEW-UHFFFAOYSA-N 0.000 claims description 2
- ZQDUZOSXDGSGCV-UHFFFAOYSA-N 1-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]-4,4-dimethylpent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)(C)C)=CC=C2N=CN=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 ZQDUZOSXDGSGCV-UHFFFAOYSA-N 0.000 claims description 2
- WZFFQCIDGPMMCY-UHFFFAOYSA-N 2-amino-4-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-1-ol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(N)CO)=CC=C1OC1=CC=CC=C1 WZFFQCIDGPMMCY-UHFFFAOYSA-N 0.000 claims description 2
- NVTUOMHARHYTMI-UHFFFAOYSA-N 2-methyl-4-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-ol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)O)=CC=C1OC1=CC=CC=C1 NVTUOMHARHYTMI-UHFFFAOYSA-N 0.000 claims description 2
- CKPXQVILGNKODG-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-8-azabicyclo[3.2.1]octan-3-ol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC2(O)CC3CCC(N3)C2)=CC=C1OC1=CC=CC=C1 CKPXQVILGNKODG-UHFFFAOYSA-N 0.000 claims description 2
- CYDURSJSMIOCKA-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenylsulfanylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(SC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 CYDURSJSMIOCKA-UHFFFAOYSA-N 0.000 claims description 2
- TZLHWSPGSJUOFJ-UHFFFAOYSA-N 3-[2-[4-(4-cyclohexyloxy-3-methylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC2CCCCC2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 TZLHWSPGSJUOFJ-UHFFFAOYSA-N 0.000 claims description 2
- NYVDQRKZZFCMIO-UHFFFAOYSA-N 3-[2-[4-[4-(2-fluorophenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C(=CC=CC=2)F)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 NYVDQRKZZFCMIO-UHFFFAOYSA-N 0.000 claims description 2
- MEYCURVEJPMYHY-UHFFFAOYSA-N 3-[2-[4-[4-(3-fluorophenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=C(F)C=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 MEYCURVEJPMYHY-UHFFFAOYSA-N 0.000 claims description 2
- WPEUWJILNODGKP-UHFFFAOYSA-N 3-[2-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C4C=CN(C4=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=CC=1C#CC1(O)CCCNC1 WPEUWJILNODGKP-UHFFFAOYSA-N 0.000 claims description 2
- SXHBKCXJRZIGNK-UHFFFAOYSA-N 3-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]-1-pyrrolidin-2-ylprop-2-yn-1-ol Chemical compound C1CCNC1C(O)C#CC(C=C12)=CC=C1N=CN=C2NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 SXHBKCXJRZIGNK-UHFFFAOYSA-N 0.000 claims description 2
- PENGKXWVBHHXRX-UHFFFAOYSA-N 4,4-dimethyl-1-[4-[4-(1-phenylethoxy)anilino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C=1C=C(NC=2C3=CC(=CC=C3N=CN=2)C#CC(O)C(C)(C)C)C=CC=1OC(C)C1=CC=CC=C1 PENGKXWVBHHXRX-UHFFFAOYSA-N 0.000 claims description 2
- VFVONEYUKIPIMQ-UHFFFAOYSA-N 4-[2-[4-[4-(1-phenylethoxy)anilino]quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound C=1C=CC=CC=1C(C)OC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCOCC1 VFVONEYUKIPIMQ-UHFFFAOYSA-N 0.000 claims description 2
- HUKIAOOLWGDHNJ-UHFFFAOYSA-N 4-[2-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]ethynyl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=C4C=CN(C4=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=C1 HUKIAOOLWGDHNJ-UHFFFAOYSA-N 0.000 claims description 2
- UTIFIONYBLSHIL-UHFFFAOYSA-N 4-methylpent-1-yn-3-ol Chemical compound CC(C)C(O)C#C UTIFIONYBLSHIL-UHFFFAOYSA-N 0.000 claims description 2
- ORDHFMSELAFTIW-UHFFFAOYSA-N 5-[2-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]ethynyl]-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound CC1(C)NC(=O)OC1C#CC1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 ORDHFMSELAFTIW-UHFFFAOYSA-N 0.000 claims description 2
- PDEZDRIPAILXBH-UHFFFAOYSA-N 6-[2-(azetidin-3-yl)ethynyl]-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC1 PDEZDRIPAILXBH-UHFFFAOYSA-N 0.000 claims description 2
- RSEWIDJHGRSYSK-UHFFFAOYSA-N 6-[2-[1-(2-methoxyethyl)piperidin-3-yl]ethynyl]-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound C1N(CCOC)CCCC1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 RSEWIDJHGRSYSK-UHFFFAOYSA-N 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 201000001342 Fallopian tube cancer Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 208000033724 Malignant tumor of fallopian tubes Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 206010047741 Vulval cancer Diseases 0.000 claims description 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 2
- 208000024207 chronic leukemia Diseases 0.000 claims description 2
- 208000030381 cutaneous melanoma Diseases 0.000 claims description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- GQHYBRONBKOVKQ-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-(2-piperidin-3-ylethyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2CCC1CCCNC1 GQHYBRONBKOVKQ-UHFFFAOYSA-N 0.000 claims description 2
- MRKFJRYFEFWGAZ-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-(2-pyrrolidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCNC1 MRKFJRYFEFWGAZ-UHFFFAOYSA-N 0.000 claims description 2
- MLNQOYLGGCZALR-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-[2-(1-methylpiperidin-3-yl)ethynyl]quinazolin-4-amine Chemical compound C1N(C)CCCC1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 MLNQOYLGGCZALR-UHFFFAOYSA-N 0.000 claims description 2
- IGMLBYRCRPUJBY-JOCHJYFZSA-N n-(3-methyl-4-phenoxyphenyl)-6-[2-[(3r)-piperidin-3-yl]ethynyl]quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#C[C@H]1CCCNC1 IGMLBYRCRPUJBY-JOCHJYFZSA-N 0.000 claims description 2
- IGMLBYRCRPUJBY-QFIPXVFZSA-N n-(3-methyl-4-phenoxyphenyl)-6-[2-[(3s)-piperidin-3-yl]ethynyl]quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#C[C@@H]1CCCNC1 IGMLBYRCRPUJBY-QFIPXVFZSA-N 0.000 claims description 2
- ODXCKHIJEWSCKY-UHFFFAOYSA-N n-[1-(benzenesulfonyl)indol-5-yl]-6-[3-(4-methylpiperazin-1-yl)prop-1-ynyl]quinazolin-4-amine Chemical compound C1CN(C)CCN1CC#CC1=CC=C(N=CN=C2NC=3C=C4C=CN(C4=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=C1 ODXCKHIJEWSCKY-UHFFFAOYSA-N 0.000 claims description 2
- NAKADWFMXIXRIU-UHFFFAOYSA-N n-[2-methyl-4-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-yl]acetamide Chemical compound C12=CC(C#CC(C)(C)NC(=O)C)=CC=C2N=CN=C1NC(C=C1C)=CC=C1OC1=CC=CC=C1 NAKADWFMXIXRIU-UHFFFAOYSA-N 0.000 claims description 2
- VICBGAMCQNEKKM-UHFFFAOYSA-N n-[4-(2-fluorophenoxy)-3-methylphenyl]-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C(=CC=CC=2)F)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCNC1 VICBGAMCQNEKKM-UHFFFAOYSA-N 0.000 claims description 2
- FCCVFKMRFKBOGT-UHFFFAOYSA-N n-[4-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-yl]acetamide Chemical compound C12=CC(C#CC(NC(C)=O)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 FCCVFKMRFKBOGT-UHFFFAOYSA-N 0.000 claims description 2
- YERQJXNIAKDTHJ-UHFFFAOYSA-N n-benzyl-3-oxo-5-(4-pyrrolidin-1-ylbutyl)-1,2-dihydropyrido[1,2-a]benzimidazole-4-carboxamide Chemical compound C=12N(CCCCN3CCCC3)C3=CC=CC=C3N2CCC(=O)C=1C(=O)NCC1=CC=CC=C1 YERQJXNIAKDTHJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 201000003708 skin melanoma Diseases 0.000 claims description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 2
- 210000000626 ureter Anatomy 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046885 vaginal cancer Diseases 0.000 claims description 2
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 2
- 201000005102 vulva cancer Diseases 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- KRGZDVBNSSJVAD-UHFFFAOYSA-N 1-methyl-3-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C1N(C)CCCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=C1 KRGZDVBNSSJVAD-UHFFFAOYSA-N 0.000 claims 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- FCUOCKYPPBZIJZ-UHFFFAOYSA-N 6-[3-(1,1-dioxo-1,4-thiazinan-4-yl)prop-1-ynyl]-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCS(=O)(=O)CC1 FCUOCKYPPBZIJZ-UHFFFAOYSA-N 0.000 claims 1
- RVESWHPQOAYXIT-UHFFFAOYSA-N [3-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]-3-azabicyclo[3.1.0]hexan-6-yl]methanol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CCN2CC3C(CO)C3C2)=CC=C1OC1=CC=CC=C1 RVESWHPQOAYXIT-UHFFFAOYSA-N 0.000 claims 1
- 210000004100 adrenal gland Anatomy 0.000 claims 1
- 239000000367 immunologic factor Substances 0.000 claims 1
- LSWJHBCFGFFBFQ-UHFFFAOYSA-N n-[4-(3-fluorophenoxy)-3-methylphenyl]-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=C(F)C=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCNC1 LSWJHBCFGFFBFQ-UHFFFAOYSA-N 0.000 claims 1
- 210000002990 parathyroid gland Anatomy 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 210000000813 small intestine Anatomy 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 abstract description 2
- 230000010261 cell growth Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 128
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- 239000000243 solution Substances 0.000 description 67
- 239000000203 mixture Substances 0.000 description 62
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 56
- 239000007787 solid Substances 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 239000000460 chlorine Substances 0.000 description 36
- 239000002904 solvent Substances 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 239000012267 brine Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 22
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 description 21
- 238000003756 stirring Methods 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 150000001412 amines Chemical class 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 12
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 150000001345 alkine derivatives Chemical class 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- BTPSYIJYKXHNFL-UHFFFAOYSA-N 2-methyl-4-nitro-1-phenoxybenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 BTPSYIJYKXHNFL-UHFFFAOYSA-N 0.000 description 7
- CTPQHELSTYPIBN-UHFFFAOYSA-N 6-iodo-4-phenoxyquinazoline Chemical compound C12=CC(I)=CC=C2N=CN=C1OC1=CC=CC=C1 CTPQHELSTYPIBN-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
- BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 230000001594 aberrant effect Effects 0.000 description 6
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 6
- LBCVFHJRTLRAPA-UHFFFAOYSA-N 6-cyclobutyl-4-phenoxyquinazoline Chemical compound C1CCC1C1=CC=C(N=CN=C2OC=3C=CC=CC=3)C2=C1 LBCVFHJRTLRAPA-UHFFFAOYSA-N 0.000 description 5
- TZROPNDQXWGRBU-UHFFFAOYSA-N 6-cyclobutyl-n-(4-phenoxyphenyl)quinazolin-4-amine Chemical compound C1CCC1C1=CC=C(N=CN=C2NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=C1 TZROPNDQXWGRBU-UHFFFAOYSA-N 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229940043279 diisopropylamine Drugs 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 230000003211 malignant effect Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000012746 preparative thin layer chromatography Methods 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 4
- QIELAZSZUTUYSQ-UHFFFAOYSA-N 3-methyl-4-phenoxyaniline Chemical compound CC1=CC(N)=CC=C1OC1=CC=CC=C1 QIELAZSZUTUYSQ-UHFFFAOYSA-N 0.000 description 4
- KJFSXKMXWJHYLN-UHFFFAOYSA-N 3-methyl-4-phenoxyaniline;hydrochloride Chemical compound Cl.CC1=CC(N)=CC=C1OC1=CC=CC=C1 KJFSXKMXWJHYLN-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- LZSYEZSQCGBROG-UHFFFAOYSA-N 4-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol;hydrochloride Chemical compound Cl.C=1C=C2N=CN=C(NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCOCC1 LZSYEZSQCGBROG-UHFFFAOYSA-N 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-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
- 230000004913 activation Effects 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 4
- 150000007514 bases Chemical class 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- RWMJRMPOKXSHHI-UHFFFAOYSA-N ethenylboron Chemical compound [B]C=C RWMJRMPOKXSHHI-UHFFFAOYSA-N 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 206010020718 hyperplasia Diseases 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WOYZXEVUWXQVNV-UHFFFAOYSA-N 4-phenoxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC=CC=C1 WOYZXEVUWXQVNV-UHFFFAOYSA-N 0.000 description 3
- CBULWJGDKVZSSR-UHFFFAOYSA-N 5-ethynyl-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound CC1(C)NC(=O)OC1C#C CBULWJGDKVZSSR-UHFFFAOYSA-N 0.000 description 3
- PUGXMZKDRVGIHC-UHFFFAOYSA-N 6-iodo-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC(I)=CC=C21 PUGXMZKDRVGIHC-UHFFFAOYSA-N 0.000 description 3
- BTZNHWJCYCFIIT-UHFFFAOYSA-N 6-iodo-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound CC1=CC(NC=2C3=CC(I)=CC=C3N=CN=2)=CC=C1OC1=CC=CC=C1 BTZNHWJCYCFIIT-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 3
- 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 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- GRTFHTWSNYAKSB-UHFFFAOYSA-N methyl 3-(4-phenoxyquinazolin-6-yl)prop-2-enoate Chemical compound C12=CC(C=CC(=O)OC)=CC=C2N=CN=C1OC1=CC=CC=C1 GRTFHTWSNYAKSB-UHFFFAOYSA-N 0.000 description 3
- YANYNYKLAALJDY-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-(3-piperazin-1-ylprop-1-ynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCNCC1 YANYNYKLAALJDY-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- KVQQRGWPQMNQQS-UHFFFAOYSA-N 1-(5-amino-2-phenoxyphenyl)ethanone Chemical compound CC(=O)C1=CC(N)=CC=C1OC1=CC=CC=C1 KVQQRGWPQMNQQS-UHFFFAOYSA-N 0.000 description 2
- BHOSCKKNURHTND-UHFFFAOYSA-N 1-(benzenesulfonyl)indol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BHOSCKKNURHTND-UHFFFAOYSA-N 0.000 description 2
- NZHIOJQVUSFMMO-UHFFFAOYSA-N 1-methyl-2-nitro-3-phenoxybenzene Chemical compound CC1=CC=CC(OC=2C=CC=CC=2)=C1[N+]([O-])=O NZHIOJQVUSFMMO-UHFFFAOYSA-N 0.000 description 2
- 125000005976 1-phenylethyloxy group Chemical group 0.000 description 2
- RDOLEWQLJCIPED-UHFFFAOYSA-N 1-pyrrolidin-2-ylprop-2-yn-1-ol Chemical compound C#CC(O)C1CCCN1 RDOLEWQLJCIPED-UHFFFAOYSA-N 0.000 description 2
- OXGPEZQSENCQFW-UHFFFAOYSA-N 2-chloro-n-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]acetamide Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CCNC(=O)CCl)=CC=C1OC1=CC=CC=C1 OXGPEZQSENCQFW-UHFFFAOYSA-N 0.000 description 2
- QFFRWDQQEDVPJM-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCNC1 QFFRWDQQEDVPJM-UHFFFAOYSA-N 0.000 description 2
- KFJFBKCMYYAWHI-UHFFFAOYSA-N 3-chloro-4-phenoxyaniline Chemical compound ClC1=CC(N)=CC=C1OC1=CC=CC=C1 KFJFBKCMYYAWHI-UHFFFAOYSA-N 0.000 description 2
- KWCSBLONIXHMSA-UHFFFAOYSA-N 3-ethyl-4-phenoxyaniline Chemical compound CCC1=CC(N)=CC=C1OC1=CC=CC=C1 KWCSBLONIXHMSA-UHFFFAOYSA-N 0.000 description 2
- DTGLFWPILMLNLT-UHFFFAOYSA-N 3-methyl-4-phenylsulfanylaniline Chemical compound CC1=CC(N)=CC=C1SC1=CC=CC=C1 DTGLFWPILMLNLT-UHFFFAOYSA-N 0.000 description 2
- GXPSEFHENUNPKG-UHFFFAOYSA-N 3-phenyl-1h-indazol-6-amine Chemical compound N=1NC2=CC(N)=CC=C2C=1C1=CC=CC=C1 GXPSEFHENUNPKG-UHFFFAOYSA-N 0.000 description 2
- DQTQWVYXTGICMC-UHFFFAOYSA-N 4,4-dimethyl-5-(2-trimethylsilylethynyl)-1,3-oxazolidin-2-one Chemical compound CC1(C)NC(=O)OC1C#C[Si](C)(C)C DQTQWVYXTGICMC-UHFFFAOYSA-N 0.000 description 2
- JDBJUUOYWBLBAZ-UHFFFAOYSA-N 4-[2-(4-chloroquinazolin-6-yl)ethynyl]oxan-4-ol Chemical compound C=1C=C2N=CN=C(Cl)C2=CC=1C#CC1(O)CCOCC1 JDBJUUOYWBLBAZ-UHFFFAOYSA-N 0.000 description 2
- WEUJVTMLARVDRA-UHFFFAOYSA-N 4-amino-4-methyl-1-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(O)C(C)(C)N)=CC=C1OC1=CC=CC=C1 WEUJVTMLARVDRA-UHFFFAOYSA-N 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- TZQVSGOOKNNDFU-UHFFFAOYSA-N 4-phenylsulfanylaniline Chemical compound C1=CC(N)=CC=C1SC1=CC=CC=C1 TZQVSGOOKNNDFU-UHFFFAOYSA-N 0.000 description 2
- KVYCTNXJMNFHHJ-UHFFFAOYSA-N 5-[2-(4-chloroquinazolin-6-yl)ethynyl]-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound CC1(C)NC(=O)OC1C#CC1=CC=C(N=CN=C2Cl)C2=C1 KVYCTNXJMNFHHJ-UHFFFAOYSA-N 0.000 description 2
- DYXKUCHKZUSDEJ-UHFFFAOYSA-N 5-nitro-2-phenoxyphenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 DYXKUCHKZUSDEJ-UHFFFAOYSA-N 0.000 description 2
- MXIWPBDHLNPTQI-UHFFFAOYSA-N 6-nitro-3-phenyl-1h-indazole Chemical compound N=1NC2=CC([N+](=O)[O-])=CC=C2C=1C1=CC=CC=C1 MXIWPBDHLNPTQI-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 2
- 206010034299 Penile cancer Diseases 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010046431 Urethral cancer Diseases 0.000 description 2
- WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 201000005188 adrenal gland cancer Diseases 0.000 description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- IAAASNBKIHCSJH-UHFFFAOYSA-N ethyl 4-oxo-2,3-dihydropyran-2-carboxylate Chemical compound CCOC(=O)C1CC(=O)C=CO1 IAAASNBKIHCSJH-UHFFFAOYSA-N 0.000 description 2
- MECFFZNWFZDTRY-UHFFFAOYSA-N ethyl 4-oxooxane-2-carboxylate Chemical compound CCOC(=O)C1CC(=O)CCO1 MECFFZNWFZDTRY-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000002390 hyperplastic effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- IGMLBYRCRPUJBY-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCNC1 IGMLBYRCRPUJBY-UHFFFAOYSA-N 0.000 description 2
- PBWLFCCQMSHXBU-UHFFFAOYSA-N n-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]-2-morpholin-4-ylacetamide Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCNC(=O)CN1CCOCC1 PBWLFCCQMSHXBU-UHFFFAOYSA-N 0.000 description 2
- XMDZINKHKMDTSD-UHFFFAOYSA-N n-[4-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]-2-methylbut-3-yn-2-yl]acetamide Chemical compound C12=CC(C#CC(C)(C)NC(=O)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 XMDZINKHKMDTSD-UHFFFAOYSA-N 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940080818 propionamide Drugs 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 201000010174 renal carcinoma Diseases 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 2
- INUWDZDWSJJFSQ-UHFFFAOYSA-N tert-butyl 4-ethynylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C#C)CC1 INUWDZDWSJJFSQ-UHFFFAOYSA-N 0.000 description 2
- JXLSDCIHYQAXOA-UHFFFAOYSA-N tert-butyl n-(2-methyl-1-oxopropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)C=O JXLSDCIHYQAXOA-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- HRPHZUAPQWJPCZ-UHFFFAOYSA-N (2-chloro-5-nitrophenyl)-phenylmethanone Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C(=O)C=2C=CC=CC=2)=C1 HRPHZUAPQWJPCZ-UHFFFAOYSA-N 0.000 description 1
- KCUFYNWXGCNJJK-UHFFFAOYSA-N (2-ethynyl-2-hydroxycyclohexyl)carbamic acid Chemical compound OC(=O)NC1CCCCC1(O)C#C KCUFYNWXGCNJJK-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- QHOXZGGIGLNFTM-QPJJXVBHSA-N (e)-3-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]prop-2-en-1-ol Chemical compound C12=CC(/C=C/CO)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 QHOXZGGIGLNFTM-QPJJXVBHSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- LMBDNXPISFBEHA-UHFFFAOYSA-N 1-(3-azabicyclo[3.1.0]hexan-6-yl)prop-2-yn-1-ol Chemical compound C1NCC2C(C(C#C)O)C21 LMBDNXPISFBEHA-UHFFFAOYSA-N 0.000 description 1
- IUAFKLWCODTXIO-UHFFFAOYSA-N 1-(4-prop-2-ynylpiperazin-1-yl)ethanone Chemical compound CC(=O)N1CCN(CC#C)CC1 IUAFKLWCODTXIO-UHFFFAOYSA-N 0.000 description 1
- VDWLCYCWLIKWBV-UHFFFAOYSA-N 1-(benzenesulfonyl)indole Chemical class C1=CC2=CC=CC=C2N1S(=O)(=O)C1=CC=CC=C1 VDWLCYCWLIKWBV-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
- BXRHEWUVAIRNDU-UHFFFAOYSA-N 1-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]cyclohexan-1-ol Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCCCC1)O BXRHEWUVAIRNDU-UHFFFAOYSA-N 0.000 description 1
- XSUSQDARHUXFQA-UHFFFAOYSA-N 1-[3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]azetidin-1-yl]ethanone Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CN(C(C)=O)C1 XSUSQDARHUXFQA-UHFFFAOYSA-N 0.000 description 1
- RCFFLGXUFOOQAF-UHFFFAOYSA-N 1-[3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-1-yl]ethanone Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCN(C(C)=O)C1 RCFFLGXUFOOQAF-UHFFFAOYSA-N 0.000 description 1
- VLZOEVZSOPFBRO-UHFFFAOYSA-N 1-[3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]azetidin-1-yl]ethanone Chemical compound C1N(C(=O)C)CC1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 VLZOEVZSOPFBRO-UHFFFAOYSA-N 0.000 description 1
- XLYNNGDJEAUYIX-UHFFFAOYSA-N 1-[3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-1-yl]ethanone Chemical compound C1N(C(=O)C)CCCC1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 XLYNNGDJEAUYIX-UHFFFAOYSA-N 0.000 description 1
- MAVCNKNKVGXNPL-UHFFFAOYSA-N 1-[3-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCCC1=O MAVCNKNKVGXNPL-UHFFFAOYSA-N 0.000 description 1
- UQELEWSBEMTABP-UHFFFAOYSA-N 1-[3-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCC1=O UQELEWSBEMTABP-UHFFFAOYSA-N 0.000 description 1
- PQVZGWMJASAZEN-UHFFFAOYSA-N 1-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCCC1=O PQVZGWMJASAZEN-UHFFFAOYSA-N 0.000 description 1
- YGCLHPYZCIDGNS-UHFFFAOYSA-N 1-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCC1=O YGCLHPYZCIDGNS-UHFFFAOYSA-N 0.000 description 1
- ZSMBEXBKWVFULH-UHFFFAOYSA-N 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCCC1=O ZSMBEXBKWVFULH-UHFFFAOYSA-N 0.000 description 1
- WZMXHVVORLTIFB-UHFFFAOYSA-N 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-4-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCC(=O)CC1 WZMXHVVORLTIFB-UHFFFAOYSA-N 0.000 description 1
- YJVNVNFZZWRBPK-UHFFFAOYSA-N 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCC1=O YJVNVNFZZWRBPK-UHFFFAOYSA-N 0.000 description 1
- CJYFGRJNPFXAOI-UHFFFAOYSA-N 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCC(O)C1 CJYFGRJNPFXAOI-UHFFFAOYSA-N 0.000 description 1
- PBAJCPLEZNNSLG-UHFFFAOYSA-N 1-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)CC)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 PBAJCPLEZNNSLG-UHFFFAOYSA-N 0.000 description 1
- OVQVJLCULNFGKP-UHFFFAOYSA-N 1-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)CC)=CC=C2N=CN=C1NC(C=C1OC)=CC=C1OC1=CC=CC=C1 OVQVJLCULNFGKP-UHFFFAOYSA-N 0.000 description 1
- OQQBQAUXQNXFSP-UHFFFAOYSA-N 1-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]-4,4-dimethylpent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)(C)C)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 OQQBQAUXQNXFSP-UHFFFAOYSA-N 0.000 description 1
- MZXXJPCDNBJWAN-UHFFFAOYSA-N 1-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C1=C2N(S(=O)(=O)C(C)C)C=CC2=CC(NC2=NC=NC3=CC=C(C=C32)C#CC(O)CC)=C1 MZXXJPCDNBJWAN-UHFFFAOYSA-N 0.000 description 1
- WOMLKPIADIEJJZ-UHFFFAOYSA-N 1-[4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-3,6-dihydro-2h-pyridin-1-yl]ethanone Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1=CCN(C(C)=O)CC1 WOMLKPIADIEJJZ-UHFFFAOYSA-N 0.000 description 1
- QQXQGCHJBXZQSA-UHFFFAOYSA-N 1-[4-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 QQXQGCHJBXZQSA-UHFFFAOYSA-N 0.000 description 1
- GAGIWSWBKBRAHA-UHFFFAOYSA-N 1-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]-4-methylpent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)C)=CC=C2N=CN=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 GAGIWSWBKBRAHA-UHFFFAOYSA-N 0.000 description 1
- BXBNWKVFKBBLKN-UHFFFAOYSA-N 1-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)CC)=CC=C2N=CN=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 BXBNWKVFKBBLKN-UHFFFAOYSA-N 0.000 description 1
- ZHJLFSPLZXBYFC-UHFFFAOYSA-N 1-[5-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-3,4-dihydro-2h-pyridin-1-yl]ethanone Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1=CN(C(C)=O)CCC1 ZHJLFSPLZXBYFC-UHFFFAOYSA-N 0.000 description 1
- JBVKDIHXGMJXMU-UHFFFAOYSA-N 1-[5-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-3,6-dihydro-2h-pyridin-1-yl]ethanone Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1=CCCN(C(C)=O)C1 JBVKDIHXGMJXMU-UHFFFAOYSA-N 0.000 description 1
- SVECTEIOAGNASD-UHFFFAOYSA-N 1-[5-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-3,4-dihydro-2h-pyridin-1-yl]ethanone Chemical compound CC(=O)N1CCCC(C#CC=2C=C3C(NC=4C=C(C)C(OC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=C1 SVECTEIOAGNASD-UHFFFAOYSA-N 0.000 description 1
- UYDNPZLYDODKKA-UHFFFAOYSA-N 1-benzylindol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 UYDNPZLYDODKKA-UHFFFAOYSA-N 0.000 description 1
- BOFKTESKTVVBIQ-UHFFFAOYSA-N 1-cyclobutyl-3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-yn-1-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC(O)C1CCC1 BOFKTESKTVVBIQ-UHFFFAOYSA-N 0.000 description 1
- XLBPREGEBTWNFZ-UHFFFAOYSA-N 1-cyclobutyl-3-[4-(4-phenoxyanilino)quinazolin-6-yl]prop-2-yn-1-ol Chemical compound C1(CCC1)C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC=C(C=C1)OC1=CC=CC=C1)O XLBPREGEBTWNFZ-UHFFFAOYSA-N 0.000 description 1
- LRISJWAVGFKCLQ-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(4-phenoxyanilino)quinazolin-6-yl]prop-2-yn-1-ol Chemical compound C1(CC1)C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC=C(C=C1)OC1=CC=CC=C1)O LRISJWAVGFKCLQ-UHFFFAOYSA-N 0.000 description 1
- AGCVOFGPTYXARD-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]prop-2-yn-1-ol Chemical compound CC(C)S(=O)(=O)n1ccc2cc(Nc3ncnc4ccc(cc34)C#CC(O)C3CC3)ccc12 AGCVOFGPTYXARD-UHFFFAOYSA-N 0.000 description 1
- XUCYJGMIICONES-UHFFFAOYSA-N 1-fluoro-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1F XUCYJGMIICONES-UHFFFAOYSA-N 0.000 description 1
- HQELYKDRJZQNBC-UHFFFAOYSA-N 1-methoxy-2-methyl-4-[4-(4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-ol Chemical compound C12=CC(C#CC(C)(O)COC)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 HQELYKDRJZQNBC-UHFFFAOYSA-N 0.000 description 1
- WCOYPFBMFKXWBM-UHFFFAOYSA-N 1-methyl-2-phenoxybenzene Chemical compound CC1=CC=CC=C1OC1=CC=CC=C1 WCOYPFBMFKXWBM-UHFFFAOYSA-N 0.000 description 1
- GSDVVSGZCXYJGG-UHFFFAOYSA-N 1-methyl-3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound CN1CC(CCC1)(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C GSDVVSGZCXYJGG-UHFFFAOYSA-N 0.000 description 1
- HVYSGDKQRPSYCS-UHFFFAOYSA-N 1-methyl-4-[2-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C1CN(C)CCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 HVYSGDKQRPSYCS-UHFFFAOYSA-N 0.000 description 1
- UDBJEKPTBHRPOS-UHFFFAOYSA-N 1-methyl-4-[2-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound CN1CCC(CC1)(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC=1C=C2C=CN(C2=CC=1)S(=O)(=O)C(C)C UDBJEKPTBHRPOS-UHFFFAOYSA-N 0.000 description 1
- TYXQHKOYIHZBNM-UHFFFAOYSA-N 1-methyl-4-[2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C1CN(C)CCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OCC=4N=CC=CC=4)=CC=3)C2=C1 TYXQHKOYIHZBNM-UHFFFAOYSA-N 0.000 description 1
- NOXAORINZJERRC-UHFFFAOYSA-N 1-methyl-4-prop-2-ynylpiperazine Chemical compound CN1CCN(CC#C)CC1 NOXAORINZJERRC-UHFFFAOYSA-N 0.000 description 1
- SRIPOKJTTBKCGL-UHFFFAOYSA-N 1-methylsulfonyl-4-prop-2-ynylpiperazine Chemical compound CS(=O)(=O)N1CCN(CC#C)CC1 SRIPOKJTTBKCGL-UHFFFAOYSA-N 0.000 description 1
- ZYWSXGRMDPBISP-UHFFFAOYSA-N 1-nitro-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC1=CC=CC=C1 ZYWSXGRMDPBISP-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- UGOQKSGJGCADAG-UHFFFAOYSA-N 1-prop-2-ynylimidazole Chemical compound C#CCN1C=CN=C1 UGOQKSGJGCADAG-UHFFFAOYSA-N 0.000 description 1
- SIYJFRXEYQGHPD-UHFFFAOYSA-N 1-prop-2-ynylpiperidin-3-ol Chemical compound OC1CCCN(CC#C)C1 SIYJFRXEYQGHPD-UHFFFAOYSA-N 0.000 description 1
- RMHJYIMLQALGFS-UHFFFAOYSA-N 1-prop-2-ynylpiperidin-4-amine Chemical compound NC1CCN(CC#C)CC1 RMHJYIMLQALGFS-UHFFFAOYSA-N 0.000 description 1
- CEUZTHSDJADUSJ-UHFFFAOYSA-N 1-prop-2-ynylpiperidin-4-ol Chemical compound OC1CCN(CC#C)CC1 CEUZTHSDJADUSJ-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BJNDYJBOLZLFPS-UHFFFAOYSA-N 2,2,2-trifluoro-N-[2-methyl-4-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-yl]acetamide Chemical compound CC(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)(C)NC(C(F)(F)F)=O BJNDYJBOLZLFPS-UHFFFAOYSA-N 0.000 description 1
- MQXDYFFSZNHJNI-UHFFFAOYSA-N 2,2-dimethyl-n-prop-2-ynylpropanamide Chemical compound CC(C)(C)C(=O)NCC#C MQXDYFFSZNHJNI-UHFFFAOYSA-N 0.000 description 1
- JYXNAPIOQIVIQU-UHFFFAOYSA-N 2-(1-prop-2-ynylpiperidin-4-yl)ethanol Chemical compound OCCC1CCN(CC#C)CC1 JYXNAPIOQIVIQU-UHFFFAOYSA-N 0.000 description 1
- BBAKZIFQVQEPIK-UHFFFAOYSA-N 2-(2-tert-butylsilyloxypropan-2-yl)-4-ethynyloxan-4-ol Chemical compound CC(C)(C)[SiH2]OC(C)(C)C1CC(O)(C#C)CCO1 BBAKZIFQVQEPIK-UHFFFAOYSA-N 0.000 description 1
- VRGRIBNDRSCFIB-UHFFFAOYSA-N 2-(2-tert-butylsilyloxypropan-2-yl)oxan-4-ol Chemical compound CC(C)(C)[SiH2]OC(C)(C)C1CC(O)CCO1 VRGRIBNDRSCFIB-UHFFFAOYSA-N 0.000 description 1
- RMWKBOCYCIHIQZ-UHFFFAOYSA-N 2-(2-tert-butylsilyloxypropan-2-yl)oxan-4-one Chemical compound CC(C)(C)[SiH2]OC(C)(C)C1CC(=O)CCO1 RMWKBOCYCIHIQZ-UHFFFAOYSA-N 0.000 description 1
- JUTXOOLTBCHYDA-UHFFFAOYSA-N 2-(4-prop-2-ynylpiperazin-1-yl)ethanol Chemical compound OCCN1CCN(CC#C)CC1 JUTXOOLTBCHYDA-UHFFFAOYSA-N 0.000 description 1
- DAEBQCQIJHJNPE-UHFFFAOYSA-N 2-(benzenesulfonyl)-1h-indole Chemical class C=1C2=CC=CC=C2NC=1S(=O)(=O)C1=CC=CC=C1 DAEBQCQIJHJNPE-UHFFFAOYSA-N 0.000 description 1
- ZHHUHRMUBGAMLO-UHFFFAOYSA-N 2-(hydroxymethyl)-3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-3-ol Chemical compound OCC1OCCCC1(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C ZHHUHRMUBGAMLO-UHFFFAOYSA-N 0.000 description 1
- VMTKLZYHESQAOQ-UHFFFAOYSA-N 2-(hydroxymethyl)-4-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound OCC1OCCC(C1)(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C VMTKLZYHESQAOQ-UHFFFAOYSA-N 0.000 description 1
- ZNGHBKAYFIORHP-UHFFFAOYSA-N 2-(hydroxymethyl)oxan-4-ol Chemical compound OCC1CC(O)CCO1 ZNGHBKAYFIORHP-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- WXVVFJRSHSMEIU-UHFFFAOYSA-N 2-[1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-4-yl]ethanol Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CCN1CCC(CC1)CCO WXVVFJRSHSMEIU-UHFFFAOYSA-N 0.000 description 1
- HUPJFSAUGWZVHR-UHFFFAOYSA-N 2-[3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-1-yl]ethanol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCN(CCO)C1 HUPJFSAUGWZVHR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FKPAVGPHHCZBEB-UHFFFAOYSA-N 2-[methyl(prop-2-ynyl)amino]ethanol Chemical compound OCCN(C)CC#C FKPAVGPHHCZBEB-UHFFFAOYSA-N 0.000 description 1
- GJGKEOFTHVXFSE-UHFFFAOYSA-N 2-[methyl-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]amino]ethanol Chemical compound C12=CC(C#CCN(CCO)C)=CC=C2N=CN=C1NC(C=C1C)=CC=C1OC1=CC=CC=C1 GJGKEOFTHVXFSE-UHFFFAOYSA-N 0.000 description 1
- AXIGBYZBWPSTEC-UHFFFAOYSA-N 2-amino-1-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]cyclohexan-1-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCCC1N AXIGBYZBWPSTEC-UHFFFAOYSA-N 0.000 description 1
- CVFQTRLBRIVGBD-UHFFFAOYSA-N 2-amino-1-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]cyclohexan-1-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCCC1N CVFQTRLBRIVGBD-UHFFFAOYSA-N 0.000 description 1
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
- ZHNCFCZNOPGCNM-UHFFFAOYSA-N 2-amino-4-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-1-ol Chemical compound NC(CO)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC ZHNCFCZNOPGCNM-UHFFFAOYSA-N 0.000 description 1
- GOLGILSVWFKZRQ-UHFFFAOYSA-N 2-amino-5-iodobenzoic acid Chemical compound NC1=CC=C(I)C=C1C(O)=O GOLGILSVWFKZRQ-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- UZOBCRQUEAWJQH-UHFFFAOYSA-N 2-benzyl-1h-indole Chemical class C=1C2=CC=CC=C2NC=1CC1=CC=CC=C1 UZOBCRQUEAWJQH-UHFFFAOYSA-N 0.000 description 1
- LAUKCAVOBZFWQZ-UHFFFAOYSA-N 2-chloro-6-iodoquinazoline Chemical compound ClC1=NC2=CC=C(C=C2C=N1)I LAUKCAVOBZFWQZ-UHFFFAOYSA-N 0.000 description 1
- BMQQXFQVEJCZBU-UHFFFAOYSA-N 2-chloro-N,N-diethyl-4-[[6-[2-(3-hydroxypiperidin-3-yl)ethynyl]quinazolin-4-yl]amino]benzamide Chemical compound ClC1=C(C(=O)N(CC)CC)C=CC(=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O BMQQXFQVEJCZBU-UHFFFAOYSA-N 0.000 description 1
- NVQSYCZPMFWIJH-UHFFFAOYSA-N 2-chloro-n-[3-(4-chloroquinazolin-6-yl)prop-2-ynyl]acetamide Chemical compound N1=CN=C(Cl)C2=CC(C#CCNC(=O)CCl)=CC=C21 NVQSYCZPMFWIJH-UHFFFAOYSA-N 0.000 description 1
- WMPTYRGXBUYONY-UHFFFAOYSA-N 2-chloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC=C21 WMPTYRGXBUYONY-UHFFFAOYSA-N 0.000 description 1
- QNBVIKVODDEHDO-UHFFFAOYSA-N 2-ethoxy-4-nitro-1-phenoxybenzene Chemical compound CCOC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 QNBVIKVODDEHDO-UHFFFAOYSA-N 0.000 description 1
- MYDJJORRUJLFOF-UHFFFAOYSA-N 2-methoxy-4-nitro-1-phenoxybenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 MYDJJORRUJLFOF-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- HFDVLZREHGHPPK-UHFFFAOYSA-N 2-methyl-4-[4-(4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-ol Chemical compound C12=CC(C#CC(C)(O)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 HFDVLZREHGHPPK-UHFFFAOYSA-N 0.000 description 1
- HLGATKIGHGPTPB-UHFFFAOYSA-N 2-methyl-4-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]but-3-yn-2-ol Chemical compound C12=CC(C#CC(C)(O)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 HLGATKIGHGPTPB-UHFFFAOYSA-N 0.000 description 1
- YJJPWHXGWFDEDN-UHFFFAOYSA-N 2-methyl-n-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]propanamide Chemical compound C12=CC(C#CCNC(=O)C(C)C)=CC=C2N=CN=C1NC(C=C1C)=CC=C1OC1=CC=CC=C1 YJJPWHXGWFDEDN-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- QFZTUWOWMRNMAH-UHFFFAOYSA-N 2h-pyran-2-carboxylic acid Chemical compound OC(=O)C1OC=CC=C1 QFZTUWOWMRNMAH-UHFFFAOYSA-N 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- KFAAKHZTICEVTO-UHFFFAOYSA-N 3,5-dichloro-4-phenoxyaniline Chemical compound ClC1=CC(N)=CC(Cl)=C1OC1=CC=CC=C1 KFAAKHZTICEVTO-UHFFFAOYSA-N 0.000 description 1
- XVOHQQJCSQRJEG-UHFFFAOYSA-N 3-(hydroxymethyl)-4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCNCC1CO XVOHQQJCSQRJEG-UHFFFAOYSA-N 0.000 description 1
- KKGXUXFBNSSMKH-UHFFFAOYSA-N 3-[(6-cyclobutylquinazolin-4-yl)amino]-n,n-diethylbenzamide Chemical compound CCN(CC)C(=O)C1=CC=CC(NC=2C3=CC(=CC=C3N=CN=2)C2CCC2)=C1 KKGXUXFBNSSMKH-UHFFFAOYSA-N 0.000 description 1
- LAJJIDDDHLKSEK-UHFFFAOYSA-N 3-[2-[4-(1h-indol-5-ylamino)quinazolin-6-yl]ethyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C4C=CNC4=CC=3)C2=CC=1CCC1(O)CCCNC1 LAJJIDDDHLKSEK-UHFFFAOYSA-N 0.000 description 1
- ZWADYMRAKSOYGV-UHFFFAOYSA-N 3-[2-[4-(2-fluoro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)C2=CC=1C#CC1(O)CCCNC1 ZWADYMRAKSOYGV-UHFFFAOYSA-N 0.000 description 1
- XGPHWMHJZULPSR-UHFFFAOYSA-N 3-[2-[4-(3,5-dichloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(OC=4C=CC=CC=4)=C(Cl)C=3)C2=CC=1C#CC1(O)CCCNC1 XGPHWMHJZULPSR-UHFFFAOYSA-N 0.000 description 1
- QCYIOLCBFIJVOC-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-phenoxyanilino)-7-(2-methoxyethoxy)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=12C=C(C#CC3(O)CNCCC3)C(OCCOC)=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 QCYIOLCBFIJVOC-UHFFFAOYSA-N 0.000 description 1
- VAFQMFADZSBDKA-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-phenoxyanilino)-7-methoxyquinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=12C=C(C#CC3(O)CNCCC3)C(OC)=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 VAFQMFADZSBDKA-UHFFFAOYSA-N 0.000 description 1
- YNUCBKJJCQFDPC-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-1-methylpiperidin-3-ol Chemical compound C1N(C)CCCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=C1 YNUCBKJJCQFDPC-UHFFFAOYSA-N 0.000 description 1
- GSUHCPPAEAYAHK-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCNC1 GSUHCPPAEAYAHK-UHFFFAOYSA-N 0.000 description 1
- YNXLZCAKYLRAKO-UHFFFAOYSA-N 3-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-7-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2C(NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)=NC=NC2=CC=1C#CC1(O)CCCNC1 YNXLZCAKYLRAKO-UHFFFAOYSA-N 0.000 description 1
- KHSOZLMXDFLYRH-UHFFFAOYSA-N 3-[2-[4-(3-ethoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C(C)OC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O KHSOZLMXDFLYRH-UHFFFAOYSA-N 0.000 description 1
- YIVUEAVDQXRSHF-UHFFFAOYSA-N 3-[2-[4-(3-ethyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(CC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 YIVUEAVDQXRSHF-UHFFFAOYSA-N 0.000 description 1
- AFCWPOSGKAUEMQ-UHFFFAOYSA-N 3-[2-[4-(3-fluoro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(F)C(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCCNC1 AFCWPOSGKAUEMQ-UHFFFAOYSA-N 0.000 description 1
- UUGYMYVLKHQZPY-UHFFFAOYSA-N 3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-1-methylpiperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCN(C)C1 UUGYMYVLKHQZPY-UHFFFAOYSA-N 0.000 description 1
- FCPFYZNPMUFUHH-UHFFFAOYSA-N 3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 FCPFYZNPMUFUHH-UHFFFAOYSA-N 0.000 description 1
- NIYHIAIRKIWMLE-UHFFFAOYSA-N 3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCNC1 NIYHIAIRKIWMLE-UHFFFAOYSA-N 0.000 description 1
- KCOLKTAUBOROMC-UHFFFAOYSA-N 3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-7-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=CC=2)=NC=NC1=CC=2C#CC1(O)CCCNC1 KCOLKTAUBOROMC-UHFFFAOYSA-N 0.000 description 1
- IISMQWSKNXDBQI-UHFFFAOYSA-N 3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol;dihydrochloride Chemical compound Cl.Cl.C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 IISMQWSKNXDBQI-UHFFFAOYSA-N 0.000 description 1
- MNIIXALEXBURSO-UHFFFAOYSA-N 3-[2-[4-(3-phenylmethoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(OCC=4C=CC=CC=4)C=CC=3)C2=CC=1C#CC1(O)CCNC1 MNIIXALEXBURSO-UHFFFAOYSA-N 0.000 description 1
- DASJERAMWZZOLO-UHFFFAOYSA-N 3-[2-[4-(4-anilinoanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=CC(NC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCCNC1 DASJERAMWZZOLO-UHFFFAOYSA-N 0.000 description 1
- CELJRKSSNSTVNQ-UHFFFAOYSA-N 3-[2-[4-(4-benzyl-3-methylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(CC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 CELJRKSSNSTVNQ-UHFFFAOYSA-N 0.000 description 1
- JMYKNVMVNRNTOL-UHFFFAOYSA-N 3-[2-[4-(4-benzylanilino)quinazolin-6-yl]ethyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=CC(CC=4C=CC=CC=4)=CC=3)C2=CC=1CCC1(O)CCCNC1 JMYKNVMVNRNTOL-UHFFFAOYSA-N 0.000 description 1
- WAXPALCLUHNJPO-UHFFFAOYSA-N 3-[2-[4-(4-bromo-2,6-difluoroanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound BrC1=CC(=C(C(=C1)F)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O)F WAXPALCLUHNJPO-UHFFFAOYSA-N 0.000 description 1
- PMXIFVBHFDUFSU-UHFFFAOYSA-N 3-[2-[4-(4-bromo-2-fluoroanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound BrC1=CC(=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O)F PMXIFVBHFDUFSU-UHFFFAOYSA-N 0.000 description 1
- QXBQZCRYSFFLLS-UHFFFAOYSA-N 3-[2-[4-(4-cyclobutyloxy-3-methylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C1(CCC1)OC1=C(C=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O)C QXBQZCRYSFFLLS-UHFFFAOYSA-N 0.000 description 1
- XOCRDHJWBNPOOV-UHFFFAOYSA-N 3-[2-[4-(4-cyclopentyloxy-3-methylanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC2CCCC2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 XOCRDHJWBNPOOV-UHFFFAOYSA-N 0.000 description 1
- QGDAGJRMCWXSSS-UHFFFAOYSA-N 3-[2-[4-(4-phenoxyanilino)quinazolin-7-yl]ethynyl]piperidin-3-ol Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC(=CC=C12)C#CC1(CNCCC1)O QGDAGJRMCWXSSS-UHFFFAOYSA-N 0.000 description 1
- PNABPEMYGBJNSJ-UHFFFAOYSA-N 3-[2-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCC1)O PNABPEMYGBJNSJ-UHFFFAOYSA-N 0.000 description 1
- OONGQXQALCPDNW-UHFFFAOYSA-N 3-[2-[4-[(1-benzylindol-5-yl)amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C(C1=CC=CC=C1)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O OONGQXQALCPDNW-UHFFFAOYSA-N 0.000 description 1
- RVERGEDWTXFIQM-UHFFFAOYSA-N 3-[2-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N(S(=O)(=O)C(C)C)C=CC2=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 RVERGEDWTXFIQM-UHFFFAOYSA-N 0.000 description 1
- GBNMTCBZSHIXBP-UHFFFAOYSA-N 3-[2-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound CC(C)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCC1)O GBNMTCBZSHIXBP-UHFFFAOYSA-N 0.000 description 1
- GHJQUHJVMJOOHO-UHFFFAOYSA-N 3-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound ClC=1C=C(C=CC1OCC1=NC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O GHJQUHJVMJOOHO-UHFFFAOYSA-N 0.000 description 1
- JQZDQNJODNZBNW-UHFFFAOYSA-N 3-[2-[4-[3-methyl-4-(2-methylphenoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound CC1=CC=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=C(C#CC3(O)CNCCC3)C=C12 JQZDQNJODNZBNW-UHFFFAOYSA-N 0.000 description 1
- OLKHXZMXRGUCIX-UHFFFAOYSA-N 3-[2-[4-[3-methyl-4-(3-methylphenoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound CC1=CC=CC(OC=2C(=CC(NC=3C4=CC(=CC=C4N=CN=3)C#CC3(O)CNCCC3)=CC=2)C)=C1 OLKHXZMXRGUCIX-UHFFFAOYSA-N 0.000 description 1
- HLFBFUIYKOAJEJ-UHFFFAOYSA-N 3-[2-[4-[3-methyl-4-(4-methylphenoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C1=CC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=C(C#CC3(O)CNCCC3)C=C12 HLFBFUIYKOAJEJ-UHFFFAOYSA-N 0.000 description 1
- NXEACUFILNZLPE-UHFFFAOYSA-N 3-[2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 NXEACUFILNZLPE-UHFFFAOYSA-N 0.000 description 1
- KXEYQHBSRNKFHF-UHFFFAOYSA-N 3-[2-[4-[4-(2-methoxyphenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound COC1=C(OC2=C(C=C(C=C2)NC2=NC=NC3=CC=C(C=C23)C#CC2(CNCCC2)O)C)C=CC=C1 KXEYQHBSRNKFHF-UHFFFAOYSA-N 0.000 description 1
- ZCWORJHSBQLWMS-UHFFFAOYSA-N 3-[2-[4-[4-(3-methoxyphenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound COC1=CC=CC(OC=2C(=CC(NC=3C4=CC(=CC=C4N=CN=3)C#CC3(O)CNCCC3)=CC=2)C)=C1 ZCWORJHSBQLWMS-UHFFFAOYSA-N 0.000 description 1
- LQKAAXFRPZWSTM-UHFFFAOYSA-N 3-[2-[4-[4-(4-fluorophenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCCNC1 LQKAAXFRPZWSTM-UHFFFAOYSA-N 0.000 description 1
- NOHKARBQHLZXCT-UHFFFAOYSA-N 3-[2-[4-[4-(4-methoxyphenoxy)-3-methylanilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C1=CC(OC)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=C(C#CC3(O)CNCCC3)C=C12 NOHKARBQHLZXCT-UHFFFAOYSA-N 0.000 description 1
- YCQXIGMBEWIFLD-UHFFFAOYSA-N 3-[2-[4-[4-(benzenesulfonyl)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C1(=CC=CC=C1)S(=O)(=O)C1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCCC1)O YCQXIGMBEWIFLD-UHFFFAOYSA-N 0.000 description 1
- MELGIYYOQQEUSR-UHFFFAOYSA-N 3-[2-[4-[4-(pyridin-2-ylmethyl)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=CC(CC=4N=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCCNC1 MELGIYYOQQEUSR-UHFFFAOYSA-N 0.000 description 1
- WMUNFAOELNBCQT-UHFFFAOYSA-N 3-[2-[4-[4-phenoxy-3-(trifluoromethyl)anilino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(C(OC=4C=CC=CC=4)=CC=3)C(F)(F)F)C2=CC=1C#CC1(O)CCCNC1 WMUNFAOELNBCQT-UHFFFAOYSA-N 0.000 description 1
- TXOUPZPKCVOZHR-UHFFFAOYSA-N 3-[2-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1(CNCC1)O TXOUPZPKCVOZHR-UHFFFAOYSA-N 0.000 description 1
- FPOBZPQKMFZAGO-UHFFFAOYSA-N 3-[2-[4-[[1-[(2-fluorophenyl)methyl]indazol-5-yl]amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound FC1=C(CN2N=CC3=CC(=CC=C23)NC2=NC=NC3=CC=C(C=C23)C#CC2(CNCCC2)O)C=CC=C1 FPOBZPQKMFZAGO-UHFFFAOYSA-N 0.000 description 1
- JMPININLEHHMSF-UHFFFAOYSA-N 3-[2-[4-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound FC=1C=C(CN2N=CC3=CC(=CC=C23)NC2=NC=NC3=CC=C(C=C23)C#CC2(CNCCC2)O)C=CC=1 JMPININLEHHMSF-UHFFFAOYSA-N 0.000 description 1
- SWDLJJRPJKRKBY-UHFFFAOYSA-N 3-[2-[4-[[1-[(3-methylphenyl)methyl]indazol-5-yl]amino]quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound CC=1C=C(CN2N=CC3=CC(=CC=C23)NC2=NC=NC3=CC=C(C=C23)C#CC2(CNCCC2)O)C=CC=1 SWDLJJRPJKRKBY-UHFFFAOYSA-N 0.000 description 1
- GFQPGJJTKHYOEG-UHFFFAOYSA-N 3-[2-[7-(2-methoxyethoxy)-4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=12C=C(C#CC3(O)CNCCC3)C(OCCOC)=CC2=NC=NC=1NC(C=C1OC)=CC=C1OC1=CC=CC=C1 GFQPGJJTKHYOEG-UHFFFAOYSA-N 0.000 description 1
- OHLQDBGUOYCVJD-UHFFFAOYSA-N 3-[2-[7-(2-methoxyethoxy)-4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=12C=C(C#CC3(O)CNCCC3)C(OCCOC)=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=C1 OHLQDBGUOYCVJD-UHFFFAOYSA-N 0.000 description 1
- DEBJFVJIEPHYEL-UHFFFAOYSA-N 3-[2-[7-methoxy-4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound C=12C=C(C#CC3(O)CNCCC3)C(OC)=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=C1 DEBJFVJIEPHYEL-UHFFFAOYSA-N 0.000 description 1
- MFPHIPKPIPRJEV-UHFFFAOYSA-N 3-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynylamino]propane-1,2-diol Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CCNCC(O)CO)=CC=C1OC1=CC=CC=C1 MFPHIPKPIPRJEV-UHFFFAOYSA-N 0.000 description 1
- JEEOCVDCSSPGCX-UHFFFAOYSA-N 3-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-2-ylprop-2-yn-1-ol Chemical compound C1CCCNC1C(O)C#CC(C=C12)=CC=C1N=CN=C2NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 JEEOCVDCSSPGCX-UHFFFAOYSA-N 0.000 description 1
- AGQLFRGNDDCAHV-UHFFFAOYSA-N 3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-2-ylprop-2-yn-1-ol Chemical compound COC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC(O)C1NCCCC1 AGQLFRGNDDCAHV-UHFFFAOYSA-N 0.000 description 1
- ONKYMWGKRCCOBM-UHFFFAOYSA-N 3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-3-ylprop-2-yn-1-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC(O)C1CCCNC1 ONKYMWGKRCCOBM-UHFFFAOYSA-N 0.000 description 1
- MSSRLRVNILDALL-UHFFFAOYSA-N 3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-2-ylprop-2-yn-1-ol Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC(O)C1NCCCC1 MSSRLRVNILDALL-UHFFFAOYSA-N 0.000 description 1
- JCHRHSJKIUEKSY-UHFFFAOYSA-N 3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-3-ylprop-2-yn-1-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC(O)C1CCCNC1 JCHRHSJKIUEKSY-UHFFFAOYSA-N 0.000 description 1
- HQRDWXSAVPRKBW-UHFFFAOYSA-N 3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]-1-pyrrolidin-2-ylprop-2-yn-1-ol Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC(O)C1NCCC1 HQRDWXSAVPRKBW-UHFFFAOYSA-N 0.000 description 1
- DPVCMQFJEOOLCJ-UHFFFAOYSA-N 3-[4-(4-phenoxyanilino)quinazolin-6-yl]-1-piperidin-3-ylprop-2-yn-1-ol Chemical compound C1CCNCC1C(O)C#CC(C=C12)=CC=C1N=CN=C2NC(C=C1)=CC=C1OC1=CC=CC=C1 DPVCMQFJEOOLCJ-UHFFFAOYSA-N 0.000 description 1
- VYSBBMKMINYUOU-UHFFFAOYSA-N 3-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]-1-pyrrolidin-2-ylprop-2-yn-1-ol Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC(O)C1NCCC1 VYSBBMKMINYUOU-UHFFFAOYSA-N 0.000 description 1
- POFTVCQGIZTAMC-UHFFFAOYSA-N 3-bromo-4-phenoxyaniline Chemical compound BrC1=CC(N)=CC=C1OC1=CC=CC=C1 POFTVCQGIZTAMC-UHFFFAOYSA-N 0.000 description 1
- UDOCSSDKTWXXSL-UHFFFAOYSA-N 3-ethoxy-4-phenoxyaniline Chemical compound CCOC1=CC(N)=CC=C1OC1=CC=CC=C1 UDOCSSDKTWXXSL-UHFFFAOYSA-N 0.000 description 1
- SYUZQKSUMLAOIB-UHFFFAOYSA-N 3-fluoro-4-phenoxyaniline Chemical compound FC1=CC(N)=CC=C1OC1=CC=CC=C1 SYUZQKSUMLAOIB-UHFFFAOYSA-N 0.000 description 1
- QYQRHZMLIRUHDJ-UHFFFAOYSA-N 3-methoxy-4-phenoxyaniline Chemical compound COC1=CC(N)=CC=C1OC1=CC=CC=C1 QYQRHZMLIRUHDJ-UHFFFAOYSA-N 0.000 description 1
- GWYHXMIMEVBRDG-UHFFFAOYSA-N 3-methoxy-4-phenoxyaniline;hydrochloride Chemical compound Cl.COC1=CC(N)=CC=C1OC1=CC=CC=C1 GWYHXMIMEVBRDG-UHFFFAOYSA-N 0.000 description 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- MYUWRMWGSCHEGM-UHFFFAOYSA-N 3-methyl-4-(4-methylphenoxy)aniline Chemical compound C1=CC(C)=CC=C1OC1=CC=C(N)C=C1C MYUWRMWGSCHEGM-UHFFFAOYSA-N 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
- JPUWOCLJCLHLTB-UHFFFAOYSA-N 4,4-dimethoxy-1-prop-2-ynylpiperidine Chemical compound COC1(OC)CCN(CC#C)CC1 JPUWOCLJCLHLTB-UHFFFAOYSA-N 0.000 description 1
- MFBLBSZMZQFQEV-UHFFFAOYSA-N 4,4-dimethyl-1-[4-(4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)(C)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 MFBLBSZMZQFQEV-UHFFFAOYSA-N 0.000 description 1
- XPNIIGOSYOBOQR-UHFFFAOYSA-N 4,4-dimethyl-1-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)(C)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 XPNIIGOSYOBOQR-UHFFFAOYSA-N 0.000 description 1
- YJAGQXQIHJHZHA-UHFFFAOYSA-N 4,4-dimethyl-5-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-1,3-oxazolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1OC(=O)NC1(C)C YJAGQXQIHJHZHA-UHFFFAOYSA-N 0.000 description 1
- KOAMXHRRVFDWRQ-UHFFFAOYSA-N 4,4-dimethyl-5h-1,3-oxazole Chemical compound CC1(C)COC=N1 KOAMXHRRVFDWRQ-UHFFFAOYSA-N 0.000 description 1
- ILPLTEOGHOQFHJ-UHFFFAOYSA-N 4,4-dimethylpent-1-yn-3-ol Chemical compound CC(C)(C)C(O)C#C ILPLTEOGHOQFHJ-UHFFFAOYSA-N 0.000 description 1
- CKPNVNAKQGYUSK-UHFFFAOYSA-N 4,6-dichloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1Cl CKPNVNAKQGYUSK-UHFFFAOYSA-N 0.000 description 1
- DQFOHACVRMWHGE-UHFFFAOYSA-N 4-(aminomethyl)-1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidin-3-ol Chemical compound NCC1C(CN(C1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)O DQFOHACVRMWHGE-UHFFFAOYSA-N 0.000 description 1
- GRRWNBJRFZQISJ-UHFFFAOYSA-N 4-(benzenesulfinyl)aniline Chemical compound C1=CC(N)=CC=C1S(=O)C1=CC=CC=C1 GRRWNBJRFZQISJ-UHFFFAOYSA-N 0.000 description 1
- UCGJCVWDWRMVSB-UHFFFAOYSA-N 4-(benzenesulfonyl)-3-methylaniline Chemical compound CC1=CC(N)=CC=C1S(=O)(=O)C1=CC=CC=C1 UCGJCVWDWRMVSB-UHFFFAOYSA-N 0.000 description 1
- GDYFDXDATVPPDR-UHFFFAOYSA-N 4-(benzenesulfonyl)aniline Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=CC=C1 GDYFDXDATVPPDR-UHFFFAOYSA-N 0.000 description 1
- WBWFQPGDDGOJDV-UHFFFAOYSA-N 4-[2-[4-(1h-indol-5-ylamino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C4C=CNC4=CC=3)C2=CC=1C#CC1(O)CCOCC1 WBWFQPGDDGOJDV-UHFFFAOYSA-N 0.000 description 1
- GCKBZSQGLXZAGJ-UHFFFAOYSA-N 4-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=C1 GCKBZSQGLXZAGJ-UHFFFAOYSA-N 0.000 description 1
- OTVWMVPRGMEMPU-UHFFFAOYSA-N 4-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-2-(hydroxymethyl)oxan-4-ol Chemical compound ClC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CC(OCC1)CO)O OTVWMVPRGMEMPU-UHFFFAOYSA-N 0.000 description 1
- OLBSXZJFHYIZCE-UHFFFAOYSA-N 4-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound ClC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CC(NC1)C(=O)N)O OLBSXZJFHYIZCE-UHFFFAOYSA-N 0.000 description 1
- ZUWNYVODNQOQBE-UHFFFAOYSA-N 4-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound ClC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCOCC1)O ZUWNYVODNQOQBE-UHFFFAOYSA-N 0.000 description 1
- HYEXTDHGXFHPQD-UHFFFAOYSA-N 4-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C=1C=C2N=CN=C(NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCNCC1 HYEXTDHGXFHPQD-UHFFFAOYSA-N 0.000 description 1
- TWHOFIXPUVYJKJ-UHFFFAOYSA-N 4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound COC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCOCC1)O TWHOFIXPUVYJKJ-UHFFFAOYSA-N 0.000 description 1
- PJAXRIVBZCJWIK-UHFFFAOYSA-N 4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CCNCC1 PJAXRIVBZCJWIK-UHFFFAOYSA-N 0.000 description 1
- RHRXZLSTGKIKPS-UHFFFAOYSA-N 4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC(=O)C1 RHRXZLSTGKIKPS-UHFFFAOYSA-N 0.000 description 1
- SCLUTSKSVNUHED-UHFFFAOYSA-N 4-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC(=O)C1 SCLUTSKSVNUHED-UHFFFAOYSA-N 0.000 description 1
- MJDQWCIVTNBQOH-UHFFFAOYSA-N 4-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound C=1C=C2N=CN=C(NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=CC=1C#CC1(O)CCOCC1 MJDQWCIVTNBQOH-UHFFFAOYSA-N 0.000 description 1
- NIKVLFZSUUHGMF-UHFFFAOYSA-N 4-[2-[4-(4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-4-ol Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCNCC1)O NIKVLFZSUUHGMF-UHFFFAOYSA-N 0.000 description 1
- HDXBVMCGTMJJGX-UHFFFAOYSA-N 4-[2-[4-(4-phenoxyanilino)quinazolin-7-yl]ethynyl]oxan-4-ol Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC(=CC=C12)C#CC1(CCOCC1)O HDXBVMCGTMJJGX-UHFFFAOYSA-N 0.000 description 1
- GJLPNJUXCYXVEU-UHFFFAOYSA-N 4-[2-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCOCC1)O GJLPNJUXCYXVEU-UHFFFAOYSA-N 0.000 description 1
- JNXCINAOMUUMPI-UHFFFAOYSA-N 4-[2-[4-[(1-benzylindol-5-yl)amino]quinazolin-6-yl]ethynyl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C#CC1=CC=C(N=CN=C2NC=3C=C4C=CN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 JNXCINAOMUUMPI-UHFFFAOYSA-N 0.000 description 1
- ICURGMZCZIIYCB-UHFFFAOYSA-N 4-[2-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound CC(C)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCOCC1)O ICURGMZCZIIYCB-UHFFFAOYSA-N 0.000 description 1
- KQQVNPNFLTVAOH-UHFFFAOYSA-N 4-[2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-6-yl]ethynyl]oxan-4-ol Chemical compound CC=1C=C(C=CC1OCC1=NC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1(CCOCC1)O KQQVNPNFLTVAOH-UHFFFAOYSA-N 0.000 description 1
- NQIAUEPSOSRCFK-UHFFFAOYSA-N 4-[2-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-7-yl]ethynyl]oxan-4-ol Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=CC=C12)C#CC1(CCOCC1)O NQIAUEPSOSRCFK-UHFFFAOYSA-N 0.000 description 1
- MAXZXQNODNDRIW-UHFFFAOYSA-N 4-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazine-1-carboxamide Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CCN1CCN(CC1)C(=O)N MAXZXQNODNDRIW-UHFFFAOYSA-N 0.000 description 1
- AMWRXCCWGDUGEN-UHFFFAOYSA-N 4-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]-2-methylbut-3-yn-2-ol Chemical compound C12=CC(C#CC(C)(O)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 AMWRXCCWGDUGEN-UHFFFAOYSA-N 0.000 description 1
- LJQZBIUVDMJDLU-UHFFFAOYSA-N 4-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-1-(methylamino)but-3-yn-2-ol Chemical compound C12=CC(C#CC(O)CNC)=CC=C2N=CN=C1NC(C=C1OC)=CC=C1OC1=CC=CC=C1 LJQZBIUVDMJDLU-UHFFFAOYSA-N 0.000 description 1
- JKBDPOVNYIMENU-UHFFFAOYSA-N 4-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-2-methylbut-3-yn-2-ol Chemical compound COC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)O)=CC=C1OC1=CC=CC=C1 JKBDPOVNYIMENU-UHFFFAOYSA-N 0.000 description 1
- JHNXLFYAHFWCPV-UHFFFAOYSA-N 4-[4-(4-phenoxyanilino)quinazolin-6-yl]-2-pyridin-3-ylbut-3-yn-2-ol Chemical compound CC(O)(C#Cc1ccc2ncnc(Nc3ccc(Oc4ccccc4)cc3)c2c1)c1cccnc1 JHNXLFYAHFWCPV-UHFFFAOYSA-N 0.000 description 1
- ADRZKLDDIOYXJP-UHFFFAOYSA-N 4-[4-(4-phenoxyanilino)quinazolin-6-yl]-2-pyridin-4-ylbut-3-yn-2-ol Chemical compound CC(O)(C#Cc1ccc2ncnc(Nc3ccc(Oc4ccccc4)cc3)c2c1)c1ccncc1 ADRZKLDDIOYXJP-UHFFFAOYSA-N 0.000 description 1
- LPRGVYCUIPGMJZ-UHFFFAOYSA-N 4-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]-2-pyridin-3-ylbut-3-yn-2-ol Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC(C)(O)C=1C=NC=CC=1 LPRGVYCUIPGMJZ-UHFFFAOYSA-N 0.000 description 1
- JYVNEUSUJWIZOS-UHFFFAOYSA-N 4-amino-1-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]-4-methylpent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)(N)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 JYVNEUSUJWIZOS-UHFFFAOYSA-N 0.000 description 1
- HSIMPYCGVBGYSD-UHFFFAOYSA-N 4-amino-1-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(N)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 HSIMPYCGVBGYSD-UHFFFAOYSA-N 0.000 description 1
- GVQHOHAWDJPYQE-UHFFFAOYSA-N 4-amino-1-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC)O)C GVQHOHAWDJPYQE-UHFFFAOYSA-N 0.000 description 1
- IIWSOWZYDRLJSX-UHFFFAOYSA-N 4-amino-1-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)O)C IIWSOWZYDRLJSX-UHFFFAOYSA-N 0.000 description 1
- NHHXMINKPQCSJD-UHFFFAOYSA-N 4-amino-1-[4-(4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC=C(C=C1)OC1=CC=CC=C1)O)C NHHXMINKPQCSJD-UHFFFAOYSA-N 0.000 description 1
- RJWGOQHVAQJPIW-UHFFFAOYSA-N 4-amino-1-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC=1C=C2C=CN(C2=CC=1)S(=O)(=O)C(C)C)O)C RJWGOQHVAQJPIW-UHFFFAOYSA-N 0.000 description 1
- CAWFATAUVLVDGP-UHFFFAOYSA-N 4-amino-1-[4-[4-(3-fluorophenoxy)-3-methylanilino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC(=CC=C1)F)C)O)C CAWFATAUVLVDGP-UHFFFAOYSA-N 0.000 description 1
- JGDFAUJDBAGWQC-UHFFFAOYSA-N 4-amino-1-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound NC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC=1C=C2C=CN(C2=CC=1)S(=O)(=O)C1=CC=CC=C1)O)C JGDFAUJDBAGWQC-UHFFFAOYSA-N 0.000 description 1
- WYFHNFGGFJJYGJ-UHFFFAOYSA-N 4-aminopent-1-yn-3-ol Chemical compound CC(N)C(O)C#C WYFHNFGGFJJYGJ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- ABKPONTYAGFVGI-UHFFFAOYSA-N 4-ethynyl-4-hydroxyoxane-2-carboxamide Chemical compound NC(=O)C1CC(O)(C#C)CCO1 ABKPONTYAGFVGI-UHFFFAOYSA-N 0.000 description 1
- SWJWVPMUAUALKX-UHFFFAOYSA-N 4-ethynyloxan-4-ol Chemical compound C#CC1(O)CCOCC1 SWJWVPMUAUALKX-UHFFFAOYSA-N 0.000 description 1
- NAPQYCWQRYDBNK-UHFFFAOYSA-N 4-hydroxy-4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxane-2-carboxamide Chemical compound OC1(CC(OCC1)C(=O)N)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC NAPQYCWQRYDBNK-UHFFFAOYSA-N 0.000 description 1
- VARCCLYZIQMRMT-UHFFFAOYSA-N 4-hydroxy-4-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidine-2-carboxamide Chemical compound OC1(CC(NC1)C(=O)N)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC VARCCLYZIQMRMT-UHFFFAOYSA-N 0.000 description 1
- OQCSBZVPTCEYGU-UHFFFAOYSA-N 4-hydroxy-4-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]oxane-2-carboxamide Chemical compound OC1(CC(OCC1)C(=O)N)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C OQCSBZVPTCEYGU-UHFFFAOYSA-N 0.000 description 1
- QCTZKDUYTQWRFX-UHFFFAOYSA-N 4-methyl-1-[4-(4-phenoxyanilino)quinazolin-6-yl]pent-1-yn-3-ol Chemical compound C12=CC(C#CC(O)C(C)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 QCTZKDUYTQWRFX-UHFFFAOYSA-N 0.000 description 1
- RGDKCWYZNRSMRU-UHFFFAOYSA-N 4-methyl-1-[4-[(1-propan-2-ylsulfonylindol-5-yl)amino]quinazolin-6-yl]pent-1-yn-3-ol Chemical compound CC(C(C#CC=1C=C2C(=NC=NC2=CC=1)NC=1C=C2C=CN(C2=CC=1)S(=O)(=O)C(C)C)O)C RGDKCWYZNRSMRU-UHFFFAOYSA-N 0.000 description 1
- JBEZZNXVDNPPOE-UHFFFAOYSA-N 4-methyl-2-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynylamino]pentan-1-ol Chemical compound C12=CC(C#CCNC(CO)CC(C)C)=CC=C2N=CN=C1NC(C=C1C)=CC=C1OC1=CC=CC=C1 JBEZZNXVDNPPOE-UHFFFAOYSA-N 0.000 description 1
- GLVOXGPMYXJKGS-UHFFFAOYSA-N 4-phenoxy-3-(trifluoromethyl)aniline Chemical compound FC(F)(F)C1=CC(N)=CC=C1OC1=CC=CC=C1 GLVOXGPMYXJKGS-UHFFFAOYSA-N 0.000 description 1
- DCFAIAIIVSJFJE-UHFFFAOYSA-N 4-phenoxyquinazoline Chemical compound N=1C=NC2=CC=CC=C2C=1OC1=CC=CC=C1 DCFAIAIIVSJFJE-UHFFFAOYSA-N 0.000 description 1
- MVQJYNJJYLWYOZ-UHFFFAOYSA-N 4-prop-2-ynylpiperazine-1-carboxamide Chemical compound NC(=O)N1CCN(CC#C)CC1 MVQJYNJJYLWYOZ-UHFFFAOYSA-N 0.000 description 1
- YZMWMLZGGSSZEV-UHFFFAOYSA-N 4-prop-2-ynylpiperazine-1-carboxylic acid Chemical compound OC(=O)N1CCN(CC#C)CC1 YZMWMLZGGSSZEV-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- NCPSBCGXDIMLRH-UHFFFAOYSA-N 5-(hydroxymethyl)-3-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1(O)CNC(CO)C1 NCPSBCGXDIMLRH-UHFFFAOYSA-N 0.000 description 1
- LEXJPFPTIRLGDQ-UHFFFAOYSA-N 5-(hydroxymethyl)-3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]pyrrolidin-3-ol Chemical compound OCC1CC(CN1)(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C LEXJPFPTIRLGDQ-UHFFFAOYSA-N 0.000 description 1
- CVSJTFKOUBOEER-UHFFFAOYSA-N 5-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound CC1(C)NC(=O)OC1C#CC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=C1 CVSJTFKOUBOEER-UHFFFAOYSA-N 0.000 description 1
- DTOKEIYRWFRFII-UHFFFAOYSA-N 5-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperazin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC(=O)CN1 DTOKEIYRWFRFII-UHFFFAOYSA-N 0.000 description 1
- RGYPZGOHQMYKJW-UHFFFAOYSA-N 5-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCC(=O)NC1 RGYPZGOHQMYKJW-UHFFFAOYSA-N 0.000 description 1
- LBSRDYCGIQTWDY-UHFFFAOYSA-N 5-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1OC(=O)NC1(C)C LBSRDYCGIQTWDY-UHFFFAOYSA-N 0.000 description 1
- SAICPDJBCLDECD-UHFFFAOYSA-N 5-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCC(=O)NC1 SAICPDJBCLDECD-UHFFFAOYSA-N 0.000 description 1
- FZJWJMZJFSCCNR-UHFFFAOYSA-N 5-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCC(=O)NC1 FZJWJMZJFSCCNR-UHFFFAOYSA-N 0.000 description 1
- UXKJULSRPSUSJW-UHFFFAOYSA-N 5-[2-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]ethynyl]-4,4-dimethyl-1,3-oxazolidin-2-one Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CC1C(NC(O1)=O)(C)C UXKJULSRPSUSJW-UHFFFAOYSA-N 0.000 description 1
- BQVHQDQBQQSECZ-UHFFFAOYSA-N 5-[[6-[2-(3-hydroxypiperidin-3-yl)ethynyl]quinazolin-4-yl]amino]-2-phenoxybenzonitrile Chemical compound OC1(CNCCC1)C#CC=1C=C2C(=NC=NC2=CC=1)NC=1C=CC(=C(C#N)C=1)OC1=CC=CC=C1 BQVHQDQBQQSECZ-UHFFFAOYSA-N 0.000 description 1
- MNIAKJQVYACFRT-UHFFFAOYSA-N 5-amino-2-phenoxybenzonitrile Chemical compound N#CC1=CC(N)=CC=C1OC1=CC=CC=C1 MNIAKJQVYACFRT-UHFFFAOYSA-N 0.000 description 1
- TTZNPYSLZLYZLZ-UHFFFAOYSA-N 5-amino-2-phenoxyphenol Chemical compound OC1=CC(N)=CC=C1OC1=CC=CC=C1 TTZNPYSLZLYZLZ-UHFFFAOYSA-N 0.000 description 1
- HLLUPLCYYBEAGS-UHFFFAOYSA-N 6-(3-aminoprop-1-ynyl)-n-(3-chloro-4-phenoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(C#CCN)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 HLLUPLCYYBEAGS-UHFFFAOYSA-N 0.000 description 1
- TXACXMOFIYWFBH-UHFFFAOYSA-N 6-(3-aminoprop-1-ynyl)-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CCN)=CC=C1OC1=CC=CC=C1 TXACXMOFIYWFBH-UHFFFAOYSA-N 0.000 description 1
- KOZZVYWKKROBGL-UHFFFAOYSA-N 6-(hydroxymethyl)-3-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperidin-3-ol Chemical compound OCC1CCC(CN1)(O)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C KOZZVYWKKROBGL-UHFFFAOYSA-N 0.000 description 1
- CXKPGTRWXCDZMX-UHFFFAOYSA-N 6-[2-(4-aminooxan-4-yl)ethynyl]-N-(3-methoxy-4-phenoxyphenyl)quinazolin-4-amine Chemical compound NC1(CCOCC1)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC CXKPGTRWXCDZMX-UHFFFAOYSA-N 0.000 description 1
- PFLQICLKXLKDFC-UHFFFAOYSA-N 6-[2-(4-aminooxan-4-yl)ethynyl]-N-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound NC1(CCOCC1)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C PFLQICLKXLKDFC-UHFFFAOYSA-N 0.000 description 1
- JJQLVAPTSSOUKR-UHFFFAOYSA-N 6-[2-(4-aminooxan-4-yl)ethynyl]-N-(4-phenoxyphenyl)quinazolin-4-amine Chemical compound NC1(CCOCC1)C#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC=C(C=C1)OC1=CC=CC=C1 JJQLVAPTSSOUKR-UHFFFAOYSA-N 0.000 description 1
- MCIQJELHMQQCBB-UHFFFAOYSA-N 6-[2-[1-(2-aminoethyl)piperidin-3-yl]ethynyl]-n-(3-methyl-4-phenoxyphenyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCCN(CCN)C1 MCIQJELHMQQCBB-UHFFFAOYSA-N 0.000 description 1
- GWOJKBCMPDAMCW-UHFFFAOYSA-N 6-[2-[4-(3-chloro-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperazin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNCC(=O)N1 GWOJKBCMPDAMCW-UHFFFAOYSA-N 0.000 description 1
- OPNUJOOBUTWPGR-UHFFFAOYSA-N 6-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]morpholin-3-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC(=O)CO1 OPNUJOOBUTWPGR-UHFFFAOYSA-N 0.000 description 1
- FUSUHIOAIUIPIW-UHFFFAOYSA-N 6-[2-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]ethynyl]piperazin-2-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNCC(=O)N1 FUSUHIOAIUIPIW-UHFFFAOYSA-N 0.000 description 1
- VDXNWNKJIPKZCP-UHFFFAOYSA-N 6-[2-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]ethynyl]morpholin-3-one Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNC(=O)CO1 VDXNWNKJIPKZCP-UHFFFAOYSA-N 0.000 description 1
- HZWJGAWORNKUMD-UHFFFAOYSA-N 6-[3-(methylamino)prop-1-ynyl]-n-(4-phenoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(C#CCNC)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 HZWJGAWORNKUMD-UHFFFAOYSA-N 0.000 description 1
- BBPUOYYUBFLNML-UHFFFAOYSA-N 6-chloro-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(Cl)=C2 BBPUOYYUBFLNML-UHFFFAOYSA-N 0.000 description 1
- ICFFNUFAZIZECD-UHFFFAOYSA-N 6-cyclopropyl-n-(4-phenoxyphenyl)quinazolin-4-amine Chemical compound C1CC1C1=CC=C(N=CN=C2NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=C1 ICFFNUFAZIZECD-UHFFFAOYSA-N 0.000 description 1
- GHGZJUIEJLXZAT-UHFFFAOYSA-N 6-iodo-1h-quinazolin-2-one Chemical compound O=C1NC=C2C=C(I)C=CC2=N1 GHGZJUIEJLXZAT-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FEWKGJMJIULTLC-UHFFFAOYSA-N C(C#C)N1CC2C(C2C1)CO.C(C#C)N1CCOCC1 Chemical compound C(C#C)N1CC2C(C2C1)CO.C(C#C)N1CCOCC1 FEWKGJMJIULTLC-UHFFFAOYSA-N 0.000 description 1
- IXGRKULMNHHYSO-UHFFFAOYSA-N C(C)(C)(C)[SiH2]OC(C(C#C)NC(O)=O)(C)C.C(C)(C)(C)OC(NC1(CCOCC1)C#C)=O.C(C)(C)(C)OC(=O)N1CC(C1)C#C Chemical compound C(C)(C)(C)[SiH2]OC(C(C#C)NC(O)=O)(C)C.C(C)(C)(C)OC(NC1(CCOCC1)C#C)=O.C(C)(C)(C)OC(=O)N1CC(C1)C#C IXGRKULMNHHYSO-UHFFFAOYSA-N 0.000 description 1
- FLNLVIQDBWMZAC-UHFFFAOYSA-N C1(CCC1)OC1=C(C=C(C=C1)N)C.C1(CCCC1)OC1=C(C=C(C=C1)N)C.C1(CCCCC1)OC1=C(C=C(C=C1)N)C Chemical compound C1(CCC1)OC1=C(C=C(C=C1)N)C.C1(CCCC1)OC1=C(C=C(C=C1)N)C.C1(CCCCC1)OC1=C(C=C(C=C1)N)C FLNLVIQDBWMZAC-UHFFFAOYSA-N 0.000 description 1
- HHRIMZKQOPLSOY-WKILWMFISA-N C1[C@@H](C(=O)OCC)C[C@@H]1C1=CC=C(N=CN=C2OC=3C=CC=CC=3)C2=C1 Chemical compound C1[C@@H](C(=O)OCC)C[C@@H]1C1=CC=C(N=CN=C2OC=3C=CC=CC=3)C2=C1 HHRIMZKQOPLSOY-WKILWMFISA-N 0.000 description 1
- QXFYERZFPDIILM-UHFFFAOYSA-N CC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)(C)CC(=O)N Chemical compound CC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)(C)CC(=O)N QXFYERZFPDIILM-UHFFFAOYSA-N 0.000 description 1
- IIXVSAKBWMOVCR-UHFFFAOYSA-N CC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC)CC(=O)N Chemical compound CC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC)CC(=O)N IIXVSAKBWMOVCR-UHFFFAOYSA-N 0.000 description 1
- ZWKJZGFELRDNGK-UHFFFAOYSA-N CC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1.CC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1.FC1=CC=C(OC2=C(C=C(C=C2)N)C)C=C1.FC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1 Chemical compound CC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1.CC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1.FC1=CC=C(OC2=C(C=C(C=C2)N)C)C=C1.FC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1 ZWKJZGFELRDNGK-UHFFFAOYSA-N 0.000 description 1
- QLFUBLQLEUPNIG-QHCPKHFHSA-N CNC(=O)N1[C@@H](CCCC1)C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC Chemical compound CNC(=O)N1[C@@H](CCCC1)C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC QLFUBLQLEUPNIG-QHCPKHFHSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- ZURBGSCUBASNJJ-UHFFFAOYSA-N FC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1.COC1=CC=C(OC2=C(C=C(C=C2)N)C)C=C1.COC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1.COC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1 Chemical compound FC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1.COC1=CC=C(OC2=C(C=C(C=C2)N)C)C=C1.COC=1C=C(OC2=C(C=C(C=C2)N)C)C=CC1.COC1=C(OC2=C(C=C(C=C2)N)C)C=CC=C1 ZURBGSCUBASNJJ-UHFFFAOYSA-N 0.000 description 1
- 208000009849 Female Genital Neoplasms Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- NVPBTXISNWUTNX-UHFFFAOYSA-N N-(3-chloro-4-phenoxyphenyl)-6-(2-pyrrolidin-3-ylethynyl)quinazolin-4-amine Chemical compound ClC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1CNCC1 NVPBTXISNWUTNX-UHFFFAOYSA-N 0.000 description 1
- MURBHXGNTWAWID-UHFFFAOYSA-N N-(3-methoxy-4-phenoxyphenyl)-6-(2-piperidin-2-ylethynyl)quinazolin-4-amine Chemical compound COC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1NCCCC1 MURBHXGNTWAWID-UHFFFAOYSA-N 0.000 description 1
- RAAKCAXZVWQFTD-UHFFFAOYSA-N N-(3-methoxy-4-phenoxyphenyl)-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound COC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1CNCCC1 RAAKCAXZVWQFTD-UHFFFAOYSA-N 0.000 description 1
- XQFFJKOWTXXIIX-UHFFFAOYSA-N N-(3-methoxy-4-phenoxyphenyl)-6-(3-piperazin-1-ylprop-1-ynyl)quinazolin-4-amine Chemical compound COC=1C=C(C=CC1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CCN1CCNCC1 XQFFJKOWTXXIIX-UHFFFAOYSA-N 0.000 description 1
- BCWYQZHKQOLQOO-UHFFFAOYSA-N N-(3-methoxy-4-phenoxyphenyl)-6-[3-(4-methylsulfonylpiperazin-1-yl)prop-1-ynyl]quinazolin-4-amine Chemical compound CS(=O)(=O)N1CCN(CC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC BCWYQZHKQOLQOO-UHFFFAOYSA-N 0.000 description 1
- CGVIATHEMNMWBC-UHFFFAOYSA-N N-(3-methyl-4-phenoxyphenyl)-6-(2-piperidin-2-ylethynyl)quinazolin-4-amine Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1NCCCC1 CGVIATHEMNMWBC-UHFFFAOYSA-N 0.000 description 1
- QJZLIWORIXGUKL-UHFFFAOYSA-N N-(3-methyl-4-phenoxyphenyl)-6-(2-piperidin-4-ylethynyl)quinazolin-4-amine Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1CCNCC1 QJZLIWORIXGUKL-UHFFFAOYSA-N 0.000 description 1
- QXFPQTCUGIGEHK-UHFFFAOYSA-N N-(3-methyl-4-phenoxyphenyl)-6-(3-pyrrolidin-1-ylprop-1-ynyl)quinazolin-4-amine Chemical compound CC=1C=C(C=CC=1OC1=CC=CC=C1)NC1=NC=NC2=CC=C(C=C12)C#CCN1CCCC1 QXFPQTCUGIGEHK-UHFFFAOYSA-N 0.000 description 1
- UAXSLDAKYRQUAH-UHFFFAOYSA-N N-(4-phenoxyphenyl)-6-(2-piperidin-2-ylethynyl)quinazolin-4-amine Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1NCCCC1 UAXSLDAKYRQUAH-UHFFFAOYSA-N 0.000 description 1
- IDHZQQIUJPOCBZ-UHFFFAOYSA-N N-(4-phenoxyphenyl)-6-(2-piperidin-3-ylethynyl)quinazolin-4-amine Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C#CC1CNCCC1 IDHZQQIUJPOCBZ-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- LILSSUMGBIJTEG-UHFFFAOYSA-N N-[1-(benzenesulfonyl)indol-5-yl]-6-[3-(2-piperidin-1-ylethylamino)prop-1-ynyl]quinazolin-4-amine Chemical compound C1(=CC=CC=C1)S(=O)(=O)N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C#CCNCCN1CCCCC1 LILSSUMGBIJTEG-UHFFFAOYSA-N 0.000 description 1
- JMQMSHDLIBLYKQ-UHFFFAOYSA-N N-benzylidene-3-phenylprop-2-enamide Chemical compound C(C1=CC=CC=C1)=NC(C=CC1=CC=CC=C1)=O JMQMSHDLIBLYKQ-UHFFFAOYSA-N 0.000 description 1
- GYESBNLLZKIVCE-UHFFFAOYSA-N N-methyl-4-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazine-1-carboxamide Chemical compound CNC(=O)N1CCN(CC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C GYESBNLLZKIVCE-UHFFFAOYSA-N 0.000 description 1
- GMFLCGPZABXTKF-UHFFFAOYSA-N NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C.NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C Chemical compound NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C.NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C GMFLCGPZABXTKF-UHFFFAOYSA-N 0.000 description 1
- PIHXQIIYKKGWGE-UHFFFAOYSA-N NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C.NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)Cl)(C)C Chemical compound NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C)C.NC(C#CC=1C=C2C(=NC=NC2=CC1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)Cl)(C)C PIHXQIIYKKGWGE-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- SNOHMAIEGRKEJP-RQNOJGIXSA-N O=C([C@H]1C[C@@H](C1)c1ccc2ncnc(Nc3ccc4n(ccc4c3)S(=O)(=O)c3ccccc3)c2c1)N1CCCC1 Chemical compound O=C([C@H]1C[C@@H](C1)c1ccc2ncnc(Nc3ccc4n(ccc4c3)S(=O)(=O)c3ccccc3)c2c1)N1CCCC1 SNOHMAIEGRKEJP-RQNOJGIXSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 101150093908 PDGFRB gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 230000010799 Receptor Interactions Effects 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 229920002253 Tannate Polymers 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- KNJFDYYSNYTTOT-UHFFFAOYSA-N [1-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-4-yl]methanol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCC(CO)CC1 KNJFDYYSNYTTOT-UHFFFAOYSA-N 0.000 description 1
- JVJUPZIFGZRWMR-UHFFFAOYSA-N [1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperidin-2-yl]methanol Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCCCC1CO JVJUPZIFGZRWMR-UHFFFAOYSA-N 0.000 description 1
- YTODQHLKCXWWSM-UHFFFAOYSA-N [3-[3-[4-[[1-(benzenesulfonyl)indol-5-yl]amino]quinazolin-6-yl]prop-2-ynyl]-3-azabicyclo[3.1.0]hexan-6-yl]methanol Chemical compound C1C2C(CO)C2CN1CC#CC(C=C12)=CC=C1N=CN=C2NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 YTODQHLKCXWWSM-UHFFFAOYSA-N 0.000 description 1
- QCFLPOQUAAPDJY-UHFFFAOYSA-N [Zn]C1CCC1 Chemical compound [Zn]C1CCC1 QCFLPOQUAAPDJY-UHFFFAOYSA-N 0.000 description 1
- PKKNIYTYIBSZNR-UHFFFAOYSA-N [Zn]N1CCC1 Chemical compound [Zn]N1CCC1 PKKNIYTYIBSZNR-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003140 astrocytic effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 150000005153 benzylindazoles Chemical class 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
- 230000008512 biological response 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
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- KXVUSQIDCZRUKF-UHFFFAOYSA-N bromocyclobutane Chemical compound BrC1CCC1 KXVUSQIDCZRUKF-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- WOBLPDAWNVAVAS-UHFFFAOYSA-N butyl carboxy carbonate Chemical compound CCCCOC(=O)OC(O)=O WOBLPDAWNVAVAS-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000000448 cultured tumor cell Anatomy 0.000 description 1
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- BADWIIDKTXQYLW-UHFFFAOYSA-N ethenylstannane Chemical compound [SnH3]C=C BADWIIDKTXQYLW-UHFFFAOYSA-N 0.000 description 1
- HEDYPDQJMPOVDO-UHFFFAOYSA-N ethyl 3-iodocyclobutane-1-carboxylate Chemical compound CCOC(=O)C1CC(I)C1 HEDYPDQJMPOVDO-UHFFFAOYSA-N 0.000 description 1
- XVQNCUMKCZOXIF-UHFFFAOYSA-N ethyl 4-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazine-1-carboxylate Chemical compound C(C)OC(=O)N1CCN(CC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC XVQNCUMKCZOXIF-UHFFFAOYSA-N 0.000 description 1
- BNFFIECRZZAJIL-UHFFFAOYSA-N ethyl 4-[3-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynylamino]piperidine-1-carboxylate Chemical compound C(C)OC(=O)N1CCC(CC1)NCC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)OC BNFFIECRZZAJIL-UHFFFAOYSA-N 0.000 description 1
- CHVVTFQLUVRBAE-UHFFFAOYSA-N ethyl 4-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazine-1-carboxylate Chemical compound C(C)OC(=O)N1CCN(CC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C CHVVTFQLUVRBAE-UHFFFAOYSA-N 0.000 description 1
- AXISEJDAUMMITD-UHFFFAOYSA-N ethyl 4-hydroxy-4-(2-trimethylsilylethynyl)oxane-2-carboxylate Chemical compound CCOC(=O)C1CC(O)(C#C[Si](C)(C)C)CCO1 AXISEJDAUMMITD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- KARLLBDFLHNKBO-UHFFFAOYSA-N hex-4-yn-3-ol Chemical compound CCC(O)C#CC KARLLBDFLHNKBO-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- STSIRHLSFMLGFV-UHFFFAOYSA-N methyl 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]piperazine-2-carboxylate Chemical compound COC(=O)C1N(CCNC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C STSIRHLSFMLGFV-UHFFFAOYSA-N 0.000 description 1
- UKSDOXFXCVSPTB-UHFFFAOYSA-N methyl 1-[3-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]pyrrolidine-2-carboxylate Chemical compound COC(=O)C1N(CCC1)CC#CC=1C=C2C(=NC=NC2=CC=1)NC1=CC(=C(C=C1)OC1=CC=CC=C1)C UKSDOXFXCVSPTB-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- RTNQTJJXOMJRQN-UHFFFAOYSA-N n,n-diethyl-3-[[6-(3-hydroxy-3-methylbut-1-ynyl)quinazolin-4-yl]amino]benzamide Chemical compound CCN(CC)C(=O)C1=CC=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)O)=C1 RTNQTJJXOMJRQN-UHFFFAOYSA-N 0.000 description 1
- XZISYAHJULRTFY-UHFFFAOYSA-N n-(2-methylbut-3-yn-2-yl)acetamide Chemical compound CC(=O)NC(C)(C)C#C XZISYAHJULRTFY-UHFFFAOYSA-N 0.000 description 1
- JASUCZMNJATDCX-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-(2-morpholin-2-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CNCCO1 JASUCZMNJATDCX-UHFFFAOYSA-N 0.000 description 1
- NSGWBWZQRWSGRA-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-[2-(1,2,3,4-tetrahydropyridin-5-yl)ethynyl]quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1=CNCCC1 NSGWBWZQRWSGRA-UHFFFAOYSA-N 0.000 description 1
- PFKPALIAXBMBDF-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-[2-(1-methylsulfonylpiperidin-3-yl)ethynyl]quinazolin-4-amine Chemical compound C1N(S(=O)(=O)C)CCCC1C#CC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=C1 PFKPALIAXBMBDF-UHFFFAOYSA-N 0.000 description 1
- DOKUXNKFAGKKHG-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-[2-(1-methylsulfonylpyrrolidin-3-yl)ethynyl]quinazolin-4-amine Chemical compound C1N(S(=O)(=O)C)CCC1C#CC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)C2=C1 DOKUXNKFAGKKHG-UHFFFAOYSA-N 0.000 description 1
- YKAYVTCYADZBLG-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-6-[3-(methylamino)prop-1-ynyl]quinazolin-4-amine Chemical compound C12=CC(C#CCNC)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OC1=CC=CC=C1 YKAYVTCYADZBLG-UHFFFAOYSA-N 0.000 description 1
- CGIPVNITOJWMAE-UHFFFAOYSA-N n-(3-methoxy-4-phenoxyphenyl)-6-(2-pyrrolidin-3-ylethynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(OC)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CC1CCNC1 CGIPVNITOJWMAE-UHFFFAOYSA-N 0.000 description 1
- ZXPBYPNKYLOEBP-UHFFFAOYSA-N n-(3-methoxy-4-phenoxyphenyl)-6-(3-methylbut-1-ynyl)quinazolin-4-amine Chemical compound COC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)C)=CC=C1OC1=CC=CC=C1 ZXPBYPNKYLOEBP-UHFFFAOYSA-N 0.000 description 1
- FMIMCTRXEIPCLN-UHFFFAOYSA-N n-(3-methoxy-4-phenoxyphenyl)-6-[3-(methylamino)prop-1-ynyl]quinazolin-4-amine Chemical compound C12=CC(C#CCNC)=CC=C2N=CN=C1NC(C=C1OC)=CC=C1OC1=CC=CC=C1 FMIMCTRXEIPCLN-UHFFFAOYSA-N 0.000 description 1
- JWOSRECJWVSBQP-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-(3-thiomorpholin-4-ylprop-1-ynyl)quinazolin-4-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2C#CCN1CCSCC1 JWOSRECJWVSBQP-UHFFFAOYSA-N 0.000 description 1
- FUSFFQCCJUKUQM-UHFFFAOYSA-N n-(3-methyl-4-phenoxyphenyl)-6-[2-(1-propylpiperidin-3-yl)ethynyl]quinazolin-4-amine Chemical compound C1N(CCC)CCCC1C#CC1=CC=C(N=CN=C2NC=3C=C(C)C(OC=4C=CC=CC=4)=CC=3)C2=C1 FUSFFQCCJUKUQM-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- DYXISCLYMDQZFQ-UHFFFAOYSA-N n-[1-(benzenesulfonyl)indol-5-yl]-6-(3-pyrrolidin-1-ylprop-1-ynyl)quinazolin-4-amine Chemical compound C1=CC2=CC(NC=3C4=CC(=CC=C4N=CN=3)C#CCN3CCCC3)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 DYXISCLYMDQZFQ-UHFFFAOYSA-N 0.000 description 1
- XRPROCKQXYNADT-UHFFFAOYSA-N n-[2-methyl-4-[4-(3-methyl-4-phenoxyanilino)quinazolin-6-yl]but-3-yn-2-yl]methanesulfonamide Chemical compound CC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)NS(C)(=O)=O)=CC=C1OC1=CC=CC=C1 XRPROCKQXYNADT-UHFFFAOYSA-N 0.000 description 1
- JCXCSQMVKMFOKR-UHFFFAOYSA-N n-[3-[4-(4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]acetamide Chemical compound C12=CC(C#CCNC(=O)C)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 JCXCSQMVKMFOKR-UHFFFAOYSA-N 0.000 description 1
- BIPZRALOFVKKBL-UHFFFAOYSA-N n-[4-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-2-methylbut-3-yn-2-yl]acetamide Chemical compound COC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)NC(C)=O)=CC=C1OC1=CC=CC=C1 BIPZRALOFVKKBL-UHFFFAOYSA-N 0.000 description 1
- CFBMKPWBKTVUQM-UHFFFAOYSA-N n-[4-[4-(3-methoxy-4-phenoxyanilino)quinazolin-6-yl]-2-methylbut-3-yn-2-yl]methanesulfonamide Chemical compound COC1=CC(NC=2C3=CC(=CC=C3N=CN=2)C#CC(C)(C)NS(C)(=O)=O)=CC=C1OC1=CC=CC=C1 CFBMKPWBKTVUQM-UHFFFAOYSA-N 0.000 description 1
- PMSORWUTWCTOJQ-UHFFFAOYSA-N n-ethoxy-4-phenoxyaniline Chemical compound C1=CC(NOCC)=CC=C1OC1=CC=CC=C1 PMSORWUTWCTOJQ-UHFFFAOYSA-N 0.000 description 1
- BFRWDAAXQJTOIB-UHFFFAOYSA-N n-methyl-4-prop-2-ynylpiperazine-1-carboxamide Chemical compound CNC(=O)N1CCN(CC#C)CC1 BFRWDAAXQJTOIB-UHFFFAOYSA-N 0.000 description 1
- QYBRRZGAKYEBTO-UHFFFAOYSA-N n-methyl-n-[3-[4-(4-phenoxyanilino)quinazolin-6-yl]prop-2-ynyl]acetamide Chemical compound C12=CC(C#CCN(C)C(C)=O)=CC=C2N=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 QYBRRZGAKYEBTO-UHFFFAOYSA-N 0.000 description 1
- BSOVIALCHYCZQT-UHFFFAOYSA-N n-methylpiperidine-1-carboxamide Chemical compound CNC(=O)N1CCCCC1 BSOVIALCHYCZQT-UHFFFAOYSA-N 0.000 description 1
- GYNAVKULVOETAD-UHFFFAOYSA-N n-phenoxyaniline Chemical class C=1C=CC=CC=1NOC1=CC=CC=C1 GYNAVKULVOETAD-UHFFFAOYSA-N 0.000 description 1
- KUVIRDUPAGKTER-UHFFFAOYSA-N n-phenylmethoxyaniline Chemical class C=1C=CC=CC=1CONC1=CC=CC=C1 KUVIRDUPAGKTER-UHFFFAOYSA-N 0.000 description 1
- AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical compound N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 description 1
- FYDSENXDPXGXEX-UHFFFAOYSA-N n-prop-2-ynylcyclopropanecarboxamide Chemical compound C#CCNC(=O)C1CC1 FYDSENXDPXGXEX-UHFFFAOYSA-N 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000025402 neoplasm of esophagus Diseases 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000003551 oxepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 201000003913 parathyroid carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- LBSKEFWQPNVWTP-UHFFFAOYSA-N pent-1-yn-3-ol Chemical compound CCC(O)C#C LBSKEFWQPNVWTP-UHFFFAOYSA-N 0.000 description 1
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- XIMBESZRBTVIOD-UHFFFAOYSA-N piperidine-2-carboxamide Chemical compound NC(=O)C1CCCCN1 XIMBESZRBTVIOD-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 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
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- SBWYTQQSTIUXOP-UHFFFAOYSA-N tert-butyl n-(1-hydroxy-2-methylpropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)CO SBWYTQQSTIUXOP-UHFFFAOYSA-N 0.000 description 1
- ACNRTYKOPZDRCO-UHFFFAOYSA-N tert-butyl n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC=O ACNRTYKOPZDRCO-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001583 thiepanyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 208000013066 thyroid gland cancer Diseases 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11734699P | 1999-01-27 | 1999-01-27 | |
PCT/IB1999/001934 WO2000044728A1 (en) | 1999-01-27 | 1999-12-06 | Substituted bicyclic derivatives useful as anticancer agents |
Publications (1)
Publication Number | Publication Date |
---|---|
BG105842A true BG105842A (bg) | 2002-04-30 |
Family
ID=22372402
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BG105842A BG105842A (bg) | 1999-01-27 | 2001-08-24 | Заместени бициклени производни, полезни като противоракови средства |
Country Status (45)
Families Citing this family (178)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2241324T3 (es) | 1998-10-08 | 2005-10-16 | Astrazeneca Ab | Derivados de quinazolina. |
UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
CZ303692B6 (cs) | 1999-02-10 | 2013-03-13 | Astrazeneca Ab | Chinazolinové deriváty jako inhibitory angiogeneze |
TR200201506T2 (tr) * | 1999-09-17 | 2002-10-21 | Abbott Gmbh & Co. Kg | Terapötik maddeler olarak kinaz inhibitörleri |
US7071199B1 (en) | 1999-09-17 | 2006-07-04 | Abbott Gmbh & Cco. Kg | Kinase inhibitors as therapeutic agents |
WO2001098277A2 (en) * | 2000-06-22 | 2001-12-27 | Pfizer Products Inc. | Substituted bicyclic derivatives for the treatment of abnormal cell growth |
US7371765B2 (en) | 2000-08-09 | 2008-05-13 | Astrazeneca Ab | Quinoline derivatives having VEGF inhibiting activity |
AU9598601A (en) | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
DK1370552T3 (da) * | 2001-03-23 | 2007-05-07 | Bayer Pharmaceuticals Corp | Rho-kinase-inhibitorer |
DK1370553T3 (da) * | 2001-03-23 | 2006-09-11 | Bayer Corp | Rho-kinase-inhibitorer |
EP1249451B1 (en) * | 2001-04-13 | 2006-06-21 | Pfizer Products Inc. | Bicyclic-substituted 4-amino-pyridopyrimidine derivatives |
WO2003000194A2 (en) | 2001-06-21 | 2003-01-03 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
JP2005515176A (ja) * | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
ES2295409T3 (es) * | 2001-11-30 | 2008-04-16 | Osi Pharmaceuticals, Inc. | Procedimiento para la preparacion de derivados biciclicos sustituidos para el tratamiento de crecimiento anormal de celulas. |
CA2469670A1 (en) * | 2001-12-12 | 2003-06-19 | Pfizer Products Inc. | Quinazoline derivatives for the treatment of abnormal cell growth |
JP2005516023A (ja) * | 2001-12-19 | 2005-06-02 | スミスクライン ビーチャム コーポレーション | プロテインチロシンキナーゼ阻害剤としてのチエノピリミジン化合物 |
US20030143165A1 (en) * | 2002-01-25 | 2003-07-31 | Allan Evans | NSAID-containing topical formulations that demonstrate chemopreventive activity |
PL371486A1 (en) | 2002-02-01 | 2005-06-13 | Astrazeneca Ab | Quinazoline compounds |
TW200302722A (en) * | 2002-02-13 | 2003-08-16 | Astrazeneca Ab | Therapeutic agents |
US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
DE60322212D1 (de) * | 2002-05-07 | 2008-08-28 | Neurosearch As | Neue azacyclische ethinylderivate |
AU2003234670B2 (en) * | 2002-05-24 | 2010-06-10 | Angiotech International Ag | Compositions and methods for coating medical implants |
US8313760B2 (en) * | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
JP2005538118A (ja) | 2002-08-06 | 2005-12-15 | アストラゼネカ アクチボラグ | Tie2(tek)活性を持つ縮合したピリジン及びピリミジン |
NZ540092A (en) | 2002-11-20 | 2007-06-29 | Array Biopharma Inc | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
US20040186160A1 (en) * | 2002-12-13 | 2004-09-23 | Sugen, Inc. | Hexahydro-cyclohepta-pyrrole oxindole as potent kinase inhibitors |
RU2005119172A (ru) * | 2002-12-18 | 2006-01-20 | Пфайзер Продактс Инк. (Us) | Производные 4-анилинхиназолина для лечения патологического роста клеток |
DK1585743T3 (da) * | 2002-12-19 | 2007-09-17 | Pfizer | 2-(H-indazol-6-ylamino)-benzamid forbindelser som protein kinase inhibitorer, nyttige til behandling opthalmiske sygdomme |
GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
WO2004106308A1 (en) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines and pyrido [3,4-d] pyrimidines as receptor tyrosine kinase inhibitors |
WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
AU2004253967B2 (en) | 2003-07-03 | 2010-02-18 | Cytovia, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
AR045563A1 (es) * | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
CN1882573A (zh) * | 2003-09-16 | 2006-12-20 | 阿斯利康(瑞典)有限公司 | 作为酪氨酸激酶抑制剂的喹唑啉衍生物 |
BRPI0414489A8 (pt) | 2003-09-16 | 2019-01-15 | Astrazeneca Ab | derivado de quinazolina, composição farmacêutica, uso de um derivado de quinazolina, e, processo para a preparação de um derivado de quinazolina |
GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
JP4303726B2 (ja) | 2003-11-11 | 2009-07-29 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ウレア誘導体およびその製造方法 |
GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
WO2005051871A2 (en) * | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Implantable sensors and implantable pumps and anti-scarring agents |
GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
WO2005075439A1 (en) | 2004-02-03 | 2005-08-18 | Astrazeneca Ab | Quinazoline derivatives |
WO2005094830A1 (en) * | 2004-03-30 | 2005-10-13 | Pfizer Products Inc. | Combinations of signal transduction inhibitors |
WO2005095419A1 (ja) * | 2004-04-01 | 2005-10-13 | Takeda Pharmaceutial Company Limited | チアゾロピリミジン誘導体 |
JP4134227B2 (ja) * | 2004-06-02 | 2008-08-20 | 武田薬品工業株式会社 | 縮合複素環化合物 |
MXPA06014125A (es) * | 2004-06-04 | 2007-01-31 | Astrazeneca Ab | Derivados de quinazolina en la forma de cinasas de tirosina de receptor erbb. |
AU2005290226A1 (en) * | 2004-07-16 | 2006-04-06 | Sunesis Pharmaceuticals, Inc. | Thienopyrimidines useful as Aurora kinase inhibitors |
TW200615268A (en) * | 2004-08-02 | 2006-05-16 | Osi Pharm Inc | Aryl-amino substituted pyrrolopyrimidine multi-kinase inhibiting compounds |
JP4167295B2 (ja) * | 2004-08-26 | 2008-10-15 | ファイザー・インク | プロテインキナーゼ阻害薬としてのピラゾール置換アミノへテロアリール化合物 |
WO2006021886A1 (en) * | 2004-08-26 | 2006-03-02 | Pfizer Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
UA87153C2 (ru) | 2004-08-26 | 2009-06-25 | Пфайзер Инк. | Энантиомерно чистые аминогетероарильные соединения как ингибиторы протеинкиназы |
JP4834553B2 (ja) | 2004-09-17 | 2011-12-14 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬組成物 |
US7285569B2 (en) | 2004-09-24 | 2007-10-23 | Hoff Hoffmann-La Roche Inc. | Tricycles, their manufacture and use as pharmaceutical agents |
AR050948A1 (es) | 2004-09-24 | 2006-12-06 | Hoffmann La Roche | Derivados de ftalazinona; su obtencion y su utilizacion en la fabricacion de medicamentos para el tratamiento del cancer. |
US20060107555A1 (en) * | 2004-11-09 | 2006-05-25 | Curtis Marc D | Universal snow plow adapter |
EP1838712B8 (en) | 2004-12-14 | 2011-10-12 | AstraZeneca AB | Pyrazolopyrimidine compounds as antitumor agents |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
EP1833511A4 (en) * | 2005-01-03 | 2011-01-19 | Myriad Genetics Inc | METHOD FOR TREATING BRAIN CANCER |
GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
EP3300739A3 (en) | 2005-03-31 | 2018-07-18 | Agensys, Inc. | Antibodies and related molecules that bind to 161p2f10b proteins |
JP2008535876A (ja) | 2005-04-14 | 2008-09-04 | エフ.ホフマン−ラ ロシュ アーゲー | アミノピラゾール誘導体、これらの製造、及び医薬製剤としての使用。 |
EP2444419A1 (en) | 2005-04-26 | 2012-04-25 | Pfizer Inc. | P-Cadherin antibodies |
GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
US7553964B2 (en) | 2005-06-03 | 2009-06-30 | Abbott Laboratories | Cyclobutyl amine derivatives |
US9006240B2 (en) | 2005-08-02 | 2015-04-14 | Eisai R&D Management Co., Ltd. | Method for assay on the effect of vascularization inhibitor |
ZA200802971B (en) | 2005-09-07 | 2009-10-28 | Amgen Fremont Inc | Human monoclonal antibodies to activin receptor-like kinase-1 |
ES2354457T3 (es) * | 2005-09-20 | 2011-03-15 | Astrazeneca Ab | Compuestos de 4-(1h-indazol-5-il-amino)-quinazolina como inhibidores del receptor erbb de la tirosina quinasa para el tratamiento del cáncer. |
CA2623125A1 (en) | 2005-09-20 | 2007-03-29 | Osi Pharmaceuticals, Inc. | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
EP1940825A1 (en) * | 2005-09-20 | 2008-07-09 | Astra Zeneca AB | Quinazoline derivatives as anticancer agents |
US7576110B2 (en) | 2005-09-22 | 2009-08-18 | Abbott Laboratories | Benzothiazole cyclobutyl amine derivatives |
TW200730527A (en) * | 2005-12-02 | 2007-08-16 | Takeda Pharmaceuticals Co | Fused heterocyclic compound |
WO2007063291A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
WO2007063293A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
JP2009531274A (ja) * | 2005-12-07 | 2009-09-03 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | キナーゼ阻害性ピロロピリジン化合物 |
US7572809B2 (en) | 2005-12-19 | 2009-08-11 | Hoffmann-La Roche Inc. | Isoquinoline aminopyrazole derivatives |
KR20080080395A (ko) | 2005-12-21 | 2008-09-03 | 아보트 러보러터리즈 | 항바이러스 화합물 |
US7915411B2 (en) | 2005-12-21 | 2011-03-29 | Abbott Laboratories | Anti-viral compounds |
CA2633760A1 (en) | 2005-12-21 | 2007-07-05 | Abbott Laboratories | Anti-viral compounds |
US20070231298A1 (en) * | 2006-03-31 | 2007-10-04 | Cell Genesys, Inc. | Cytokine-expressing cancer immunotherapy combinations |
AU2007251282A1 (en) | 2006-05-09 | 2007-11-22 | Pfizer Products Inc. | Cycloalkylamino acid derivatives and pharmaceutical compositions thereof |
CN101443009A (zh) | 2006-05-18 | 2009-05-27 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
KR20090024811A (ko) | 2006-06-23 | 2009-03-09 | 아보트 러보러터리즈 | 히스타민 h3 수용체 조절제로서의 사이클로프로필 아민 유도체 |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
US8865737B2 (en) | 2006-08-28 | 2014-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for undifferentiated gastric cancer |
EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
EP2103620A1 (en) | 2006-12-12 | 2009-09-23 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
CA2672737A1 (en) | 2006-12-20 | 2008-11-06 | Abbott Laboratories | Anti-viral compounds |
CA2676796C (en) | 2007-01-29 | 2016-02-23 | Eisai R & D Management Co., Ltd. | Composition for treatment of undifferentiated gastric cancer |
KR100799821B1 (ko) * | 2007-02-05 | 2008-01-31 | 동화약품공업주식회사 | 신규한 이마티닙 캠실레이트 및 그의 제조방법 |
EP2118075A1 (de) | 2007-02-06 | 2009-11-18 | Boehringer Ingelheim International GmbH | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
ES2529790T3 (es) | 2007-04-13 | 2015-02-25 | Dana-Farber Cancer Institute, Inc. | Métodos de tratamiento de cáncer resistente a agentes terapéuticos de ERBB |
WO2008127707A1 (en) * | 2007-04-13 | 2008-10-23 | Dana Farber Cancer Institute, Inc. | Receptor tyrosine kinase profiling |
US7956190B2 (en) | 2007-06-25 | 2011-06-07 | Hoffmann-La Roche Inc. | Benzimidazole amido derivatives as kinase inhibitors |
PT2185574E (pt) | 2007-09-07 | 2013-08-26 | Agensys Inc | Anticorpos e moléculas relacionadas que se ligam a proteínas 24p4c12 |
WO2009060945A1 (ja) | 2007-11-09 | 2009-05-14 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質と抗腫瘍性白金錯体との併用 |
RS52573B (en) | 2008-02-07 | 2013-04-30 | Boehringer Ingelheim International Gmbh | SPIROCYCLIC HETEROCYCLES, THE MEDICINAL PRODUCTS CONTAINING THIS UNIT, THEIR APPLICATION AND THE PROCEDURE FOR THEIR MANUFACTURING |
US7932036B1 (en) | 2008-03-12 | 2011-04-26 | Veridex, Llc | Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase |
US20090233937A1 (en) * | 2008-03-12 | 2009-09-17 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
EP2303276B1 (en) | 2008-05-13 | 2013-11-13 | AstraZeneca AB | Fumarate salt of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(n-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline |
US20110086834A1 (en) * | 2008-06-26 | 2011-04-14 | Amgen Inc. | Alkynyl alcohols as kinase inhibitors |
US20100029675A1 (en) * | 2008-07-25 | 2010-02-04 | Hwang Soo-In | Pyrimidine-2, 4-diamine JAK2 Kinase inhibiting anti-inflammation use |
CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
AR073501A1 (es) | 2008-09-08 | 2010-11-10 | Boehringer Ingelheim Int | Derivados de pirimido[5,4-d]pirimidina inhibidores de la tirosinoquinasa |
EP2241565A1 (en) | 2009-01-15 | 2010-10-20 | Universität Leipzig | Aurora kinase inhibitors compounds |
EP2393814A1 (en) * | 2009-02-09 | 2011-12-14 | SuperGen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
WO2010099137A2 (en) | 2009-02-26 | 2010-09-02 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the emt status of tumor cells in vivo |
JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
TW201035088A (en) | 2009-02-27 | 2010-10-01 | Supergen Inc | Cyclopentathiophene/cyclohexathiophene DNA methyltransferase inhibitors |
JP2012519281A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
EP2473500A2 (en) | 2009-09-01 | 2012-07-11 | Pfizer Inc. | Benzimidazole derivatives |
AU2011223655A1 (en) | 2010-03-03 | 2012-06-28 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
US20110275644A1 (en) | 2010-03-03 | 2011-11-10 | Buck Elizabeth A | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
CA2802644C (en) | 2010-06-25 | 2017-02-21 | Eisai R & D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
EP3489680B1 (en) | 2010-07-28 | 2024-07-03 | Janssen Pharmaceutica NV | Method of determining acute myeloid leukemia response to treatment with farnesyltransferase inhibitors |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
WO2012052948A1 (en) | 2010-10-20 | 2012-04-26 | Pfizer Inc. | Pyridine- 2- derivatives as smoothened receptor modulators |
KR101643721B1 (ko) * | 2010-11-09 | 2016-07-28 | 후지안 하이시 파머수티클스, 인코포레이티드 | 키나아제 활성을 증진시키기 위한 화합물 및 이의 응용 |
US20120214830A1 (en) | 2011-02-22 | 2012-08-23 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
BR112013021941B1 (pt) | 2011-04-18 | 2022-11-16 | Eisai R & D Management Co., Ltd | Agente terapêutico para tumor |
TR201905909T4 (tr) | 2011-04-19 | 2019-05-21 | Pfizer | Kanser tedavisi için anti-4-1bb antikorlarının ve adcc indükleyici antikorların kombinasyonları. |
EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
ES2841809T3 (es) | 2011-06-03 | 2021-07-09 | Eisai R&D Man Co Ltd | Biomarcadores para pronosticar y evaluar el grado de respuesta de sujetos con cáncer de tiroides y de riñón a compuestos de lenvatinib |
US9416132B2 (en) | 2011-07-21 | 2016-08-16 | Tolero Pharmaceuticals, Inc. | Substituted imidazo[1,2-b]pyridazines as protein kinase inhibitors |
AU2012311184A1 (en) | 2011-09-22 | 2014-03-06 | Pfizer Inc. | Pyrrolopyrimidine and purine derivatives |
IN2014CN04183A (cs) | 2011-11-08 | 2015-07-17 | Pfizer | |
TWI577671B (zh) * | 2011-11-14 | 2017-04-11 | Sunshine Lake Pharma Co Ltd | Aminoquinazoline derivatives and salts thereof and methods of use thereof |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
ES2644758T3 (es) | 2012-10-16 | 2017-11-30 | Tolero Pharmaceuticals, Inc. | Moduladores de PKM2 y métodos para su uso |
US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
EP2937337A4 (en) | 2012-12-21 | 2016-06-22 | Eisai R&D Man Co Ltd | AMORPHIC FORM OF CHINOLINE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF |
US9468681B2 (en) | 2013-03-01 | 2016-10-18 | California Institute Of Technology | Targeted nanoparticles |
AU2014236820B2 (en) | 2013-03-14 | 2018-08-02 | Sumitomo Pharma Oncology, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
MX368099B (es) | 2013-05-14 | 2019-09-19 | Eisai R&D Man Co Ltd | Biomarcadores para predecir y evaluar el grado de respuesta de sujetos con cancer de endometrio a compuestos de tipo lenvatinib. |
UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
CN103784412A (zh) * | 2014-01-15 | 2014-05-14 | 青岛市肿瘤医院 | 一种盐酸埃克替尼分散片及其制备方法 |
WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
PT3137460T (pt) | 2014-04-30 | 2019-12-30 | Pfizer | Derivados de di-heterociclo ligado a cicloalquilo |
WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
SI3524595T1 (sl) | 2014-08-28 | 2022-10-28 | Eisai R&D Management Co., Ltd. | Derivat kinolina visoke čistosti in postopek njegove proizvodnje |
US20180028662A1 (en) | 2015-02-25 | 2018-02-01 | Eisai R&D Management Co., Ltd. | Method for Suppressing Bitterness of Quinoline Derivative |
CA2978226A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharpe & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
WO2016172214A1 (en) | 2015-04-20 | 2016-10-27 | Tolero Pharmaceuticals, Inc. | Predicting response to alvocidib by mitochondrial profiling |
DK3298021T3 (da) | 2015-05-18 | 2019-08-05 | Tolero Pharmaceuticals Inc | Alvocidib-prodrugs, der har øget biotilgængelighed |
MX373231B (es) | 2015-06-16 | 2020-05-08 | Eisai R&D Man Co Ltd | Agente anticancerigeno. |
CN107922609B (zh) | 2015-07-01 | 2020-04-24 | 加州理工学院 | 基于阳离子粘酸聚合物的递送系统 |
WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
MX2018001289A (es) | 2015-08-03 | 2018-04-30 | Tolero Pharmaceuticals Inc | Terapias de combinacion para el tratamiento del cancer. |
KR102587702B1 (ko) | 2015-08-20 | 2023-10-12 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양 치료제 |
SG11201804360XA (en) | 2015-12-03 | 2018-06-28 | Agios Pharmaceuticals Inc | Mat2a inhibitors for treating mtap null cancer |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
CA3047557A1 (en) | 2016-12-19 | 2018-06-28 | Tolero Pharmaceuticals, Inc. | Profiling peptides and methods for sensitivity profiling |
JP6581320B2 (ja) | 2017-02-08 | 2019-09-25 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療用医薬組成物 |
MX2019013014A (es) | 2017-05-16 | 2020-08-06 | Eisai R&D Man Co Ltd | Tratamiento de carcinoma hepatocelular. |
WO2019055579A1 (en) | 2017-09-12 | 2019-03-21 | Tolero Pharmaceuticals, Inc. | TREATMENT REGIME FOR CANCERS THAT ARE INSENSITIVE TO BCL-2 INHIBITORS USING THE MCL-1 ALVOCIDIB INHIBITOR |
AU2018333913B2 (en) | 2017-09-14 | 2022-11-17 | Daiichi Sankyo Company, Limited | Compound having cyclic structure |
WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
KR20190043437A (ko) | 2017-10-18 | 2019-04-26 | 씨제이헬스케어 주식회사 | 단백질 키나제 억제제로서의 헤테로고리 화합물 |
US11708335B2 (en) | 2017-12-18 | 2023-07-25 | Sterngreene, Inc. | Pyrimidine compounds useful as tyrosine kinase inhibitors |
US20190381188A1 (en) | 2018-06-13 | 2019-12-19 | California Institute Of Technology | Nanoparticles For Crossing The Blood Brain Barrier And Methods Of Treatment Using The Same |
US11040038B2 (en) | 2018-07-26 | 2021-06-22 | Sumitomo Dainippon Pharma Oncology, Inc. | Methods for treating diseases associated with abnormal ACVR1 expression and ACVR1 inhibitors for use in the same |
SG11202102981SA (en) | 2018-09-25 | 2021-04-29 | Black Diamond Therapeutics Inc | Quinazoline derivatives as tyrosine kinase inhibitor, compositions, methods of making them and their use |
KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
US11034710B2 (en) | 2018-12-04 | 2021-06-15 | Sumitomo Dainippon Pharma Oncology, Inc. | CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer |
JP7662528B2 (ja) | 2019-02-12 | 2025-04-15 | スミトモ ファーマ アメリカ, インコーポレイテッド | 複素環式タンパク質キナーゼ阻害剤を含む製剤 |
US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
AU2020245437A1 (en) | 2019-03-22 | 2021-09-30 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
WO2021179274A1 (en) * | 2020-03-13 | 2021-09-16 | Suzhou Zanrong Pharma Ltd. | ErbB RECEPTOR INHIBITORS AS ANTI-TUMOR AGENTS |
KR102234530B1 (ko) * | 2020-09-01 | 2021-03-31 | 대한민국 | 신규 톨트라주릴 유도체 및 이를 포함하는 쿠도아충 예방·치료를 위한 약학 조성물 |
WO2022221227A1 (en) | 2021-04-13 | 2022-10-20 | Nuvalent, Inc. | Amino-substituted heterocycles for treating cancers with egfr mutations |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0222274A (ja) * | 1988-01-23 | 1990-01-25 | Kyowa Hakko Kogyo Co Ltd | ピリダジノン誘導体 |
US5034393A (en) | 1989-07-27 | 1991-07-23 | Dowelanco | Fungicidal use of pyridopyrimidine, pteridine, pyrimidopyrimidine, pyrimidopyridazine, and pyrimido-1,2,4-triazine derivatives |
US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
ES2108120T3 (es) | 1991-05-10 | 1997-12-16 | Rhone Poulenc Rorer Int | Compuestos bis arilicos y heteroarilicos mono- y biciclicos que inhiben tirosina quinasa receptora de egf y/o pdgf. |
NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
DK0612321T3 (da) * | 1991-10-09 | 1999-12-13 | Syntex Inc | Pyridopyridazinon- og pyridazinthionforbindelser med PDE IV inhiberende aktivitet |
US5256781A (en) | 1991-10-24 | 1993-10-26 | American Home Products Corporation | Substituted quinazolines as angiotensin II antagonists |
US5283242A (en) | 1991-10-24 | 1994-02-01 | American Home Products Corporation | Substituted benzimidazoles and quinazolines as antihypertensives |
AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
DK40192D0 (da) | 1992-03-26 | 1992-03-26 | Neurosearch As | Imidazolforbindelser, deres fremstilling og anvendelse |
JP2994165B2 (ja) * | 1992-06-26 | 1999-12-27 | ゼネカ・リミテッド | キナゾリン誘導体、その製造法および該キナゾリン誘導体を含有する抗癌作用を得るための医薬調剤 |
GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
MX9603593A (es) | 1994-02-23 | 1997-03-29 | Pfizer | Derivados de quinazolina. |
TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
DE69616993T2 (de) * | 1995-03-14 | 2002-07-04 | Novartis Ag, Basel | Trisubstituierte phenyl derivate |
EP0817775B1 (en) | 1995-03-30 | 2001-09-12 | Pfizer Inc. | Quinazoline derivatives |
US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
WO1996040142A1 (en) | 1995-06-07 | 1996-12-19 | Pfizer Inc. | Heterocyclic ring-fused pyrimidine derivatives |
US6140332A (en) * | 1995-07-06 | 2000-10-31 | Novartis Ag | Pyrrolopyrimidines and processes for the preparation thereof |
AR004010A1 (es) * | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
ES2260156T3 (es) | 1995-12-08 | 2006-11-01 | Janssen Pharmaceutica N.V. | Derivados de (imidazol-5-il)metil-2-quinolinona como inhibidores de la proteina farnesil-transferasa. |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
GB9603097D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline compounds |
DE19629652A1 (de) * | 1996-03-06 | 1998-01-29 | Thomae Gmbh Dr K | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
DE19608653A1 (de) * | 1996-03-06 | 1997-09-11 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
HRP970371A2 (en) * | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
AR007855A1 (es) * | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios, uso en medicinay composiciones farmaceuticas que los contienen |
ATE227283T1 (de) * | 1996-07-13 | 2002-11-15 | Glaxo Group Ltd | Kondensierte heterozyklische verbindungen als protein kinase inhibitoren |
DK0938486T3 (da) * | 1996-08-23 | 2008-07-07 | Novartis Ag | Substituerede pyrrolopyrimidiner og fremgangsmåder til deres fremstilling |
CA2239227C (en) | 1996-10-01 | 2007-10-30 | Kenji Matsuno | Nitrogen-containing heterocyclic compounds |
EP0837063A1 (en) * | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
US6413971B1 (en) * | 1996-11-27 | 2002-07-02 | Pfizer Inc | Fused bicyclic pyrimidine derivatives |
DE19653646A1 (de) | 1996-12-20 | 1998-06-25 | Hoechst Ag | Substituierte Purinderivate, Verfahren zu deren Herstellung, sie enthaltende Mittel und deren Verwendung |
JP2001522853A (ja) * | 1997-11-11 | 2001-11-20 | ファイザー・プロダクツ・インク | 抗癌剤として有用なチエノピリミジンおよびチエノピリジン誘導体 |
UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
JP3270834B2 (ja) * | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
-
1999
- 1999-06-12 UA UA2001075376A patent/UA71945C2/uk unknown
- 1999-11-23 TW TW088120466A patent/TW519541B/zh active
- 1999-11-24 MY MYPI99005119A patent/MY124390A/en unknown
- 1999-12-06 IL IL14328499A patent/IL143284A0/xx unknown
- 1999-12-06 OA OA1200100190A patent/OA11752A/en unknown
- 1999-12-06 YU YU43001A patent/YU43001A/sh unknown
- 1999-12-06 AT AT99956281T patent/ATE359275T1/de not_active IP Right Cessation
- 1999-12-06 NZ NZ511707A patent/NZ511707A/xx unknown
- 1999-12-06 KR KR10-2001-7009539A patent/KR100471953B1/ko not_active Expired - Fee Related
- 1999-12-06 HR HR20010542A patent/HRP20010542A2/hr not_active Application Discontinuation
- 1999-12-06 ES ES99956281T patent/ES2284273T3/es not_active Expired - Lifetime
- 1999-12-06 AU AU12916/00A patent/AU775163B2/en not_active Ceased
- 1999-12-06 CA CA002358998A patent/CA2358998C/en not_active Expired - Fee Related
- 1999-12-06 AP APAP/P/2001/002223A patent/AP1307A/en active
- 1999-12-06 WO PCT/IB1999/001934 patent/WO2000044728A1/en active IP Right Grant
- 1999-12-06 HK HK02105471.5A patent/HK1043795B/zh not_active IP Right Cessation
- 1999-12-06 EA EA200100553A patent/EA006107B1/ru not_active IP Right Cessation
- 1999-12-06 CZ CZ20012638A patent/CZ20012638A3/cs unknown
- 1999-12-06 BR BR9916980-0A patent/BR9916980A/pt not_active Application Discontinuation
- 1999-12-06 TR TR2001/02136T patent/TR200102136T2/xx unknown
- 1999-12-06 DE DE69935807T patent/DE69935807T2/de not_active Expired - Lifetime
- 1999-12-06 JP JP2000595984A patent/JP2002535391A/ja active Pending
- 1999-12-06 ID IDW00200101631A patent/ID29276A/id unknown
- 1999-12-06 EP EP99956281A patent/EP1147093B1/en not_active Expired - Lifetime
- 1999-12-06 GE GEAP19996018A patent/GEP20033140B/en unknown
- 1999-12-06 EE EEP200100393A patent/EE200100393A/xx unknown
- 1999-12-06 CN CNB998158259A patent/CN1182123C/zh not_active Expired - Fee Related
- 1999-12-06 HU HU0203425A patent/HUP0203425A3/hu unknown
- 1999-12-06 SK SK1018-2001A patent/SK10182001A3/sk not_active Application Discontinuation
- 1999-12-08 MA MA25863A patent/MA26712A1/fr unknown
- 1999-12-08 TN TNTNSN99236A patent/TNSN99236A1/fr unknown
- 1999-12-08 DZ DZ990263A patent/DZ2963A1/xx active
- 1999-12-13 CO CO99077826A patent/CO5080774A1/es unknown
- 1999-12-15 PE PE1999001256A patent/PE20001363A1/es not_active Application Discontinuation
- 1999-12-15 AR ARP990106428A patent/AR023346A1/es not_active Application Discontinuation
- 1999-12-17 PA PA19998487601A patent/PA8487601A1/es unknown
- 1999-12-22 SV SV1999000252A patent/SV1999000252A/es unknown
- 1999-12-29 UY UY25887A patent/UY25887A1/es unknown
- 1999-12-30 UY UY25889A patent/UY25889A1/es unknown
-
2000
- 2000-01-20 US US09/488,350 patent/US6284764B1/en not_active Expired - Fee Related
- 2000-01-26 GT GT200000005A patent/GT200000005A/es unknown
-
2001
- 2001-04-12 US US09/834,259 patent/US6541481B2/en not_active Expired - Fee Related
- 2001-05-22 IS IS5949A patent/IS5949A/is unknown
- 2001-06-27 CR CR6404A patent/CR6404A/es not_active Application Discontinuation
- 2001-07-17 ZA ZA200105867A patent/ZA200105867B/en unknown
- 2001-07-26 NO NO20013671A patent/NO322297B1/no unknown
- 2001-08-24 BG BG105842A patent/BG105842A/bg unknown
-
2003
- 2003-01-21 US US10/349,475 patent/US20030186995A1/en not_active Abandoned
-
2004
- 2004-07-23 JP JP2004216138A patent/JP2005002125A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
BG105842A (bg) | Заместени бициклени производни, полезни като противоракови средства | |
EP1029853B1 (en) | Heteroaromatic bicyclic derivatives useful as anticancer agents | |
JP4044839B2 (ja) | 異常細胞増殖を治療するための置換2環式誘導体 | |
KR100479401B1 (ko) | 항증식성 물질로 유용한 신규 벤조이미다졸 유도체 | |
US7585869B2 (en) | Substituted heterocylces for the treatment of abnormal cell growth | |
EP1396489A1 (en) | Heteroaromatic bicyclic derivatives useful as anticancer agents | |
MXPA01007585A (en) | Substituted bicyclic derivatives useful as anticancer agents |