CA2673564A1 - Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer - Google Patents
Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer Download PDFInfo
- Publication number
- CA2673564A1 CA2673564A1 CA002673564A CA2673564A CA2673564A1 CA 2673564 A1 CA2673564 A1 CA 2673564A1 CA 002673564 A CA002673564 A CA 002673564A CA 2673564 A CA2673564 A CA 2673564A CA 2673564 A1 CA2673564 A1 CA 2673564A1
- Authority
- CA
- Canada
- Prior art keywords
- fluoro
- ethyl
- benzo
- thiophen
- ylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 20
- 201000011510 cancer Diseases 0.000 title claims abstract description 12
- VLUNZXPZDFIDHY-UHFFFAOYSA-N 1-(2-aminopyrimidin-4-yl)imidazolidin-2-one Chemical class NC1=NC=CC(N2C(NCC2)=O)=N1 VLUNZXPZDFIDHY-UHFFFAOYSA-N 0.000 title abstract description 4
- -1 N- ethyl-N-methyl-aminomethyl Chemical group 0.000 claims abstract description 80
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 6
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 117
- 238000002360 preparation method Methods 0.000 claims description 64
- 238000000034 method Methods 0.000 claims description 30
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 17
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 7
- 208000006359 hepatoblastoma Diseases 0.000 claims description 7
- 210000004072 lung Anatomy 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 230000002357 endometrial effect Effects 0.000 claims description 6
- 230000002496 gastric effect Effects 0.000 claims description 6
- 208000005017 glioblastoma Diseases 0.000 claims description 6
- 230000002611 ovarian Effects 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 5
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims description 5
- 201000002510 thyroid cancer Diseases 0.000 claims description 5
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 5
- QADAGRMJDHQDKK-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-(methylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 QADAGRMJDHQDKK-UHFFFAOYSA-N 0.000 claims description 4
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- KYBIPQPSROLOCS-UHFFFAOYSA-N 1-[2-[[4-[7-[5-[(dimethylamino)methyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CN(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 KYBIPQPSROLOCS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- UYTCWUVORXVCND-UHFFFAOYSA-N 1-[2-[[4-[7-(3-ethynylpyridin-4-yl)-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound O=C1NCCN1CCNC1=NC=CC(C=2SC3=C(C=4C(=CN=CC=4)C#C)C=CC=C3C=2)=N1 UYTCWUVORXVCND-UHFFFAOYSA-N 0.000 claims description 2
- MRTYWKAMISMGLF-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(1-aminoethyl)-2-chloropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CC(N)C1=CN=C(Cl)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 MRTYWKAMISMGLF-UHFFFAOYSA-N 0.000 claims description 2
- MQYLIQZJCZPQQO-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(1-aminoethyl)-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CC(N)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 MQYLIQZJCZPQQO-UHFFFAOYSA-N 0.000 claims description 2
- NARFBCXIDVLVCW-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(aminomethyl)-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound NCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 NARFBCXIDVLVCW-UHFFFAOYSA-N 0.000 claims description 2
- JAJIISZKXLOBDG-OAHLLOKOSA-N 1-[2-[[4-[7-[5-[(1r)-1-(ethylamino)ethyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CCN[C@H](C)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 JAJIISZKXLOBDG-OAHLLOKOSA-N 0.000 claims description 2
- CUHKVGINWUYOIB-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-(2-hydroxyethoxy)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound OCCOC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 CUHKVGINWUYOIB-UHFFFAOYSA-N 0.000 claims description 2
- GJYCJMMWHUYHLC-CQSZACIVSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-[(1r)-1-(methylamino)ethyl]pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CN[C@H](C)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 GJYCJMMWHUYHLC-CQSZACIVSA-N 0.000 claims description 2
- NCJKEKAWOMTEFP-UHFFFAOYSA-N 3-[2-[[5-fluoro-4-[7-[2-fluoro-5-(methylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]-1h-imidazol-2-one Chemical compound CNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NC=C3)=O)N=1)F)=C2 NCJKEKAWOMTEFP-UHFFFAOYSA-N 0.000 claims description 2
- JMBIBCQEEKELJI-UHFFFAOYSA-N 1-[2-[[4-[7-(3-ethynylpyridin-4-yl)-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound N1=C(C=2SC3=C(C=4C(=CN=CC=4)C#C)C=CC=C3C=2)C(F)=CN=C1NCCN1CCNC1=O JMBIBCQEEKELJI-UHFFFAOYSA-N 0.000 claims 1
- CLLZTOLFNOYVOC-UHFFFAOYSA-N 1-[2-[[4-[7-(5-cyclopropyl-2-fluoropyridin-4-yl)-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1C1CC1 CLLZTOLFNOYVOC-UHFFFAOYSA-N 0.000 claims 1
- ZTAGQCAMNHODLG-UHFFFAOYSA-N 1-[2-[[4-[7-[2-fluoro-5-(methylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]-5-methylpyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)C)=C2 ZTAGQCAMNHODLG-UHFFFAOYSA-N 0.000 claims 1
- KPGCKBYQKOXSQK-UHFFFAOYSA-N 1-[2-[[4-[7-[2-fluoro-5-(methylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1N=C(NCCN3C(NCC3)=O)N=CC=1)=C2 KPGCKBYQKOXSQK-UHFFFAOYSA-N 0.000 claims 1
- FWEMIHAQEPNYDX-UHFFFAOYSA-N 1-[2-[[4-[7-[2-fluoro-5-(morpholin-4-ylmethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2N=C(NCCN3C(NCC3)=O)N=CC=2)=C1CN1CCOCC1 FWEMIHAQEPNYDX-UHFFFAOYSA-N 0.000 claims 1
- SPEXVKIVYKTBGL-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(azetidin-1-ylmethyl)-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1CN1CCC1 SPEXVKIVYKTBGL-UHFFFAOYSA-N 0.000 claims 1
- ZNPZUTQZOFKTJZ-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(diethylaminomethyl)-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CCN(CC)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 ZNPZUTQZOFKTJZ-UHFFFAOYSA-N 0.000 claims 1
- ZFEVJYDFKWYFFN-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(ethylaminomethyl)-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CCNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 ZFEVJYDFKWYFFN-UHFFFAOYSA-N 0.000 claims 1
- MQYLIQZJCZPQQO-CYBMUJFWSA-N 1-[2-[[4-[7-[5-[(1r)-1-aminoethyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C[C@@H](N)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 MQYLIQZJCZPQQO-CYBMUJFWSA-N 0.000 claims 1
- FQPAHDSPAMAWMT-UHFFFAOYSA-N 1-[2-[[4-[7-[5-[(dimethylamino)methyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-methylpyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CN(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)C)=C2 FQPAHDSPAMAWMT-UHFFFAOYSA-N 0.000 claims 1
- VYCBXJSXFLLVIW-UHFFFAOYSA-N 1-[2-[[4-[7-[5-[(dimethylamino)methyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CN(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1N=C(NCCN3C(NCC3)=O)N=CC=1)=C2 VYCBXJSXFLLVIW-UHFFFAOYSA-N 0.000 claims 1
- BKAHQNXDVGHVSS-UHFFFAOYSA-N 1-[2-[[4-[7-[5-[[ethyl(methyl)amino]methyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]-5-fluoropyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CCN(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 BKAHQNXDVGHVSS-UHFFFAOYSA-N 0.000 claims 1
- RVAQYEZJYXORDB-UHFFFAOYSA-N 1-[2-[[5-chloro-4-[7-[2-fluoro-5-(methylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)Cl)=C2 RVAQYEZJYXORDB-UHFFFAOYSA-N 0.000 claims 1
- QLDKVZSEOJYHSE-UHFFFAOYSA-N 1-[2-[[5-chloro-4-[7-[5-[(dimethylamino)methyl]-2-fluoropyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CN(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)Cl)=C2 QLDKVZSEOJYHSE-UHFFFAOYSA-N 0.000 claims 1
- JPMCFETVSVSZBE-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-3-(methoxymethoxymethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound COCOCC1=C(F)N=CC=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 JPMCFETVSVSZBE-UHFFFAOYSA-N 0.000 claims 1
- MUHNAPHSFULNDY-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-(morpholin-4-ylmethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1CN1CCOCC1 MUHNAPHSFULNDY-UHFFFAOYSA-N 0.000 claims 1
- FDTNKXWDYOPEFG-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-(propylaminomethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound CCCNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 FDTNKXWDYOPEFG-UHFFFAOYSA-N 0.000 claims 1
- RTDTWJHRQLDYJL-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-(pyrrolidin-1-ylmethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1CN1CCCC1 RTDTWJHRQLDYJL-UHFFFAOYSA-N 0.000 claims 1
- XHTLGAKMKNCTGZ-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-[(2-hydroxyethylamino)methyl]pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound OCCNCC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 XHTLGAKMKNCTGZ-UHFFFAOYSA-N 0.000 claims 1
- BHPAKJZFNGAWHR-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[2-fluoro-5-[(3,3,3-trifluoropropylamino)methyl]pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1CNCCC(F)(F)F BHPAKJZFNGAWHR-UHFFFAOYSA-N 0.000 claims 1
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- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
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- 238000009521 phase II clinical trial Methods 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- XZJPQMRGZSSYHN-UHFFFAOYSA-N propan-1-amine Chemical compound CCCN.CCCN XZJPQMRGZSSYHN-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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- 229920005989 resin Polymers 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
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- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GDQPIMNLDFXSLR-UHFFFAOYSA-N tert-butyl n-[(6-fluoro-4-iodopyridin-3-yl)methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CN=C(F)C=C1I GDQPIMNLDFXSLR-UHFFFAOYSA-N 0.000 description 1
- KQSWZIGWXPHDFK-UHFFFAOYSA-N tert-butyl n-[1-(6-chloropyridin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CC=C(Cl)N=C1 KQSWZIGWXPHDFK-UHFFFAOYSA-N 0.000 description 1
- XWZDZWSBOHKJJF-UHFFFAOYSA-N tert-butyl n-[1-[4-(1-benzothiophen-7-yl)-6-fluoropyridin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(F)C=C1C1=CC=CC2=C1SC=C2 XWZDZWSBOHKJJF-UHFFFAOYSA-N 0.000 description 1
- UMIMMMHDGHAEET-UHFFFAOYSA-N tert-butyl n-[1-[4-[2-(2-chloro-5-fluoropyrimidin-4-yl)-1-benzothiophen-7-yl]-6-fluoropyridin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(Cl)N=1)F)=C2 UMIMMMHDGHAEET-UHFFFAOYSA-N 0.000 description 1
- HYQUMFFMKPBHSC-UHFFFAOYSA-N tert-butyl n-[1-[6-chloro-4-[2-[5-fluoro-2-[2-(2-oxoimidazolidin-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(Cl)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 HYQUMFFMKPBHSC-UHFFFAOYSA-N 0.000 description 1
- LENSSPWGTFHIKH-UHFFFAOYSA-N tert-butyl n-[1-[6-fluoro-4-[2-[5-fluoro-2-[2-(2-oxo-1h-imidazol-3-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NC=C3)=O)N=1)F)=C2 LENSSPWGTFHIKH-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- MSXKECUMNGTTTR-UHFFFAOYSA-N tert-butyl n-[[4-[2-(2-chloro-5-fluoropyrimidin-4-yl)-1-benzothiophen-7-yl]-6-fluoropyridin-3-yl]methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(Cl)N=1)F)=C2 MSXKECUMNGTTTR-UHFFFAOYSA-N 0.000 description 1
- QQYQNUZNLJXCKJ-UHFFFAOYSA-N tert-butyl n-[[6-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]methyl]-n-(3,3,3-trifluoropropyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCC(F)(F)F)CC1=CN=C(F)C=C1B1OC(C)(C)C(C)(C)O1 QQYQNUZNLJXCKJ-UHFFFAOYSA-N 0.000 description 1
- NLKZTZBRGAUALL-UHFFFAOYSA-N tert-butyl n-[[6-fluoro-4-[2-[5-fluoro-2-[2-(2-oxoimidazolidin-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]methyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CC1=CN=C(F)C=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3C(NCC3)=O)N=1)F)=C2 NLKZTZBRGAUALL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87132206P | 2006-12-21 | 2006-12-21 | |
| US60/871,322 | 2006-12-21 | ||
| PCT/US2007/087046 WO2008076705A1 (en) | 2006-12-21 | 2007-12-11 | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2673564A1 true CA2673564A1 (en) | 2008-06-26 |
Family
ID=39185681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002673564A Abandoned CA2673564A1 (en) | 2006-12-21 | 2007-12-11 | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer |
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|---|---|
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| EP (1) | EP2125794B1 (enExample) |
| JP (1) | JP2010513553A (enExample) |
| KR (1) | KR101080594B1 (enExample) |
| CN (1) | CN101568539B (enExample) |
| AT (1) | ATE485291T1 (enExample) |
| AU (1) | AU2007334040B2 (enExample) |
| BR (1) | BRPI0720607A2 (enExample) |
| CA (1) | CA2673564A1 (enExample) |
| CY (1) | CY1110950T1 (enExample) |
| DE (1) | DE602007010041D1 (enExample) |
| DK (1) | DK2125794T3 (enExample) |
| EA (1) | EA016178B1 (enExample) |
| ES (1) | ES2351371T3 (enExample) |
| HR (1) | HRP20100641T1 (enExample) |
| MX (1) | MX2009006635A (enExample) |
| PL (1) | PL2125794T3 (enExample) |
| PT (1) | PT2125794E (enExample) |
| RS (1) | RS51526B (enExample) |
| SI (1) | SI2125794T1 (enExample) |
| WO (1) | WO2008076705A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE479680T1 (de) | 2006-12-21 | 2010-09-15 | Lilly Co Eli | Imidazolidinonylaminopyrimidinverbindungen zur behandlung von krebs |
| TW200908981A (en) * | 2007-05-16 | 2009-03-01 | Lilly Co Eli | Triazolyl aminopyrimidine compounds |
| CN104781257A (zh) | 2012-06-14 | 2015-07-15 | 第一三共株式会社 | 哌啶基吡唑并吡啶衍生物 |
| EP2929883A1 (en) | 2014-04-08 | 2015-10-14 | Institut Pasteur | Pyrazole derivatives as dihydroorotate dehydrogenase (DHODH) inhibitors |
| KR102693614B1 (ko) | 2022-04-04 | 2024-08-08 | 경희대학교 산학협력단 | 나프탈렌-2-일알킬기가 치환된 이미다졸리움 유도체 및 이를 유효성분으로 포함하는 암 치료용 조성물 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4929726A (en) | 1988-02-09 | 1990-05-29 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
| WO2004063192A1 (en) | 2003-01-10 | 2004-07-29 | Pharmacopeia Drug Discovery, Inc. | Imidazolyl pyrimidine derivatives useful as il-8 receptor modulators |
| GB0308466D0 (en) | 2003-04-11 | 2003-05-21 | Novartis Ag | Organic compounds |
| CN101115749B (zh) * | 2004-12-17 | 2011-06-22 | 安姆根有限公司 | 氨基嘧啶化合物和使用方法 |
| TW200800201A (en) * | 2005-11-18 | 2008-01-01 | Lilly Co Eli | Pyrimidinyl benzothiophene compounds |
| EP2001480A4 (en) * | 2006-03-31 | 2011-06-15 | Abbott Lab | Indazole CONNECTIONS |
| ATE479680T1 (de) | 2006-12-21 | 2010-09-15 | Lilly Co Eli | Imidazolidinonylaminopyrimidinverbindungen zur behandlung von krebs |
| EP2155735A2 (en) | 2007-05-16 | 2010-02-24 | Eli Lilly And Company | Triazolyl aminopyrimidine compounds |
| TW200908981A (en) | 2007-05-16 | 2009-03-01 | Lilly Co Eli | Triazolyl aminopyrimidine compounds |
-
2007
- 2007-12-11 EA EA200970616A patent/EA016178B1/ru not_active IP Right Cessation
- 2007-12-11 DK DK07855060.5T patent/DK2125794T3/da active
- 2007-12-11 PT PT07855060T patent/PT2125794E/pt unknown
- 2007-12-11 HR HR20100641T patent/HRP20100641T1/hr unknown
- 2007-12-11 DE DE602007010041T patent/DE602007010041D1/de active Active
- 2007-12-11 CA CA002673564A patent/CA2673564A1/en not_active Abandoned
- 2007-12-11 US US12/516,251 patent/US8063212B2/en not_active Expired - Fee Related
- 2007-12-11 KR KR1020097012768A patent/KR101080594B1/ko not_active Expired - Fee Related
- 2007-12-11 ES ES07855060T patent/ES2351371T3/es active Active
- 2007-12-11 AU AU2007334040A patent/AU2007334040B2/en not_active Ceased
- 2007-12-11 SI SI200730463T patent/SI2125794T1/sl unknown
- 2007-12-11 RS RSP-2010/0547A patent/RS51526B/sr unknown
- 2007-12-11 CN CN2007800477447A patent/CN101568539B/zh not_active Expired - Fee Related
- 2007-12-11 JP JP2009543062A patent/JP2010513553A/ja not_active Withdrawn
- 2007-12-11 PL PL07855060T patent/PL2125794T3/pl unknown
- 2007-12-11 MX MX2009006635A patent/MX2009006635A/es active IP Right Grant
- 2007-12-11 WO PCT/US2007/087046 patent/WO2008076705A1/en not_active Ceased
- 2007-12-11 BR BRPI0720607-0A2A patent/BRPI0720607A2/pt not_active IP Right Cessation
- 2007-12-11 AT AT07855060T patent/ATE485291T1/de active
- 2007-12-11 EP EP07855060A patent/EP2125794B1/en active Active
-
2010
- 2010-11-26 CY CY20101101083T patent/CY1110950T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN101568539B (zh) | 2012-04-25 |
| EP2125794A1 (en) | 2009-12-02 |
| MX2009006635A (es) | 2009-06-30 |
| PT2125794E (pt) | 2011-01-10 |
| CY1110950T1 (el) | 2015-06-10 |
| BRPI0720607A2 (pt) | 2014-04-08 |
| RS51526B (sr) | 2011-06-30 |
| US20100081641A1 (en) | 2010-04-01 |
| ATE485291T1 (de) | 2010-11-15 |
| HRP20100641T1 (hr) | 2010-12-31 |
| SI2125794T1 (sl) | 2011-02-28 |
| KR20090086111A (ko) | 2009-08-10 |
| EP2125794B1 (en) | 2010-10-20 |
| DE602007010041D1 (de) | 2010-12-02 |
| CN101568539A (zh) | 2009-10-28 |
| JP2010513553A (ja) | 2010-04-30 |
| EA200970616A1 (ru) | 2009-10-30 |
| DK2125794T3 (da) | 2011-01-24 |
| AU2007334040A1 (en) | 2008-06-26 |
| KR101080594B1 (ko) | 2011-11-04 |
| AU2007334040B2 (en) | 2012-02-16 |
| ES2351371T3 (es) | 2011-02-03 |
| EA016178B1 (ru) | 2012-02-28 |
| US8063212B2 (en) | 2011-11-22 |
| PL2125794T3 (pl) | 2011-04-29 |
| WO2008076705A1 (en) | 2008-06-26 |
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| AU2008254319B2 (en) | Triazolyl aminopyrimidine compounds | |
| AU2007334040B2 (en) | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer | |
| AU2008254318B2 (en) | Triazolyl aminopyrimidine compounds | |
| AU2007334039B2 (en) | Imidazolidinonyl aminopyrimidine compounds for the treatment' of cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20140617 |