HRP20100641T1 - Imidazolidinonilaminopirimidinski spojevi za liječenje raka - Google Patents
Imidazolidinonilaminopirimidinski spojevi za liječenje raka Download PDFInfo
- Publication number
- HRP20100641T1 HRP20100641T1 HR20100641T HRP20100641T HRP20100641T1 HR P20100641 T1 HRP20100641 T1 HR P20100641T1 HR 20100641 T HR20100641 T HR 20100641T HR P20100641 T HRP20100641 T HR P20100641T HR P20100641 T1 HRP20100641 T1 HR P20100641T1
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- Croatia
- Prior art keywords
- ethyl
- thiophen
- benzo
- ylamino
- imidazolidin
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract 4
- 201000011510 cancer Diseases 0.000 title claims abstract 4
- 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 2
- -1 N-ethyl-N-methyl-aminomethyl Chemical group 0.000 claims abstract 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 19
- 239000001257 hydrogen Substances 0.000 claims abstract 19
- 150000003839 salts Chemical class 0.000 claims abstract 11
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims abstract 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 2
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims abstract 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims 10
- 229910052731 fluorine Inorganic materials 0.000 claims 10
- 239000011737 fluorine Substances 0.000 claims 10
- 150000002431 hydrogen Chemical class 0.000 claims 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 229910052801 chlorine Inorganic materials 0.000 claims 4
- 239000000460 chlorine Substances 0.000 claims 4
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims 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
- 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 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
- 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
- JYGALHMZUQWTRL-UHFFFAOYSA-N 1-[2-[[4-[7-[5-(1,3-dioxolan-2-yl)-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)=C1C1OCCO1 JYGALHMZUQWTRL-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
- 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 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
- 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 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
- 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
- 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 1
- 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 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
- 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 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
- XCQRVSDFDFCBOI-UHFFFAOYSA-N 1-[2-[[5-fluoro-4-[7-[3-(morpholin-4-ylmethyl)pyridin-4-yl]-1-benzothiophen-2-yl]pyrimidin-2-yl]amino]ethyl]imidazolidin-2-one Chemical compound N1=C(C=2SC3=C(C=4C(=CN=CC=4)CN4CCOCC4)C=CC=C3C=2)C(F)=CN=C1NCCN1CCNC1=O XCQRVSDFDFCBOI-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- KUWANAHFMKBKIY-UHFFFAOYSA-N 3-[[6-fluoro-4-[2-[5-fluoro-2-[2-(2-oxoimidazolidin-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]pyridin-3-yl]methylamino]propanenitrile Chemical compound C1=NC(F)=CC(C=2C=3SC(=CC=3C=CC=2)C=2C(=CN=C(NCCN3C(NCC3)=O)N=2)F)=C1CNCCC#N KUWANAHFMKBKIY-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 206010023774 Large cell lung cancer Diseases 0.000 claims 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 claims 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 208000006359 hepatoblastoma Diseases 0.000 claims 1
- 201000009546 lung large cell carcinoma Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000006958 oropharynx cancer Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 3
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 108010056274 polo-like kinase 1 Proteins 0.000 abstract 1
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
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- 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)
Abstract
Spoj formule: naznačen time što: R1 je aminometil, (C1-C3 alkil)aminometil, di(C1-C2 alkil)aminometil, N-etil-N-metilaminometil, 1-aminoetil, 1-((C1-C2 alkil)amino)etil, 3,3,3-trifluorpropilaminometil, etinil, 2-hidroksietoksi, 2-hidroksietilaminometil, 2-cijanoetilaminometil, morfolin-4-ilmetil, metoksimetoksimetil, ciklopropil, 1-azetidinilmetil, 1-pirolidinilmetil ili 1,3-dioksolan-2-il; R2 je vodik ili halogen; R3 je vodik ili halogen; uz uvjet da najmanje jedan od R2 i R3 je vodik; R4 je vodik, metil ili halogen; i---- je jednostruka veza, koja je bilo prisutna ili odsutna, ilinjegova farmaceutski prihvatljiva sol. Patent sadrži još 9 patentnih zahtjeva.
Claims (10)
1. Spoj formule:
[image]
naznačen time što:
R1 je aminometil, (C1-C3 alkil)aminometil, di(C1-C2 alkil)aminometil, N-etil-N-metilaminometil, 1-aminoetil, 1-((C1-C2 alkil)amino)etil, 3,3,3-trifluorpropilaminometil, etinil, 2-hidroksietoksi, 2-hidroksietilaminometil, 2-cijanoetilaminometil, morfolin-4-ilmetil, metoksimetoksimetil, ciklopropil, 1-azetidinilmetil, 1-pirolidinilmetil ili 1,3-dioksolan-2-il;
R2 je vodik ili halogen;
R3 je vodik ili halogen;
uz uvjet da najmanje jedan od R2 i R3 je vodik;
R4 je vodik, metil ili halogen; i
---- je jednostruka veza, koja je bilo prisutna ili odsutna, ili
njegova farmaceutski prihvatljiva sol.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što:
R2 je vodik ili fluor;
R3 je vodik, klor ili fluor; uz uvjet da najmanje jedan od R2 i R3 je vodik; i
R4 je vodik, metil, klor ili fluor; ili
njegova farmaceutski prihvatljiva sol.
3. Spoj u skladu s patentnim zahtjevom 1, naznačen time što:
R1 je dimetilaminometil, metilaminometil ili aminometil;
R2 je vodik ili fluor;
R3 je vodik, klor ili fluor; uz uvjet da najmanje jedan od R2 i R3 je vodik; i
R4 je vodik, metil, klor ili fluor; ili
njegova farmaceutski prihvatljiva sol.
4. Spoj u skladu s patentnim zahtjevom 1, naznačen time što R1 je dimetilaminometil, R2 je vodik, R3 je fluor, a R4 je fluor, ili njegova farmaceutski prihvatljiva sol.
5. Spoj u skladu s patentnim zahtjevom 1, naznačen time što R1 je metilaminometil, R2 je vodik, R3 je fluor, a R4 je fluor, ili njegova farmaceutski prihvatljiva sol.
6. Spoj u skladu s patentnim zahtjevom 1, naznačen time što R1 je aminometil, R2 je vodik, R3 je halogen i R4 je halogen, ili njegova farmaceutski prihvatljiva sol.
7. Spoj, naznačen time što ga se bira iz skupine koju čine:
1-(2-{4-[7-(5-((Dimetilamino)metil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(2-Fluor-5-(morfolinometil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-5-(morfolinometil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(5-((Dimetilamino)metil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(3-(morfolinometil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(5-(1,3-Dioksolan-2-il)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-3-((metoksimetoksi)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(5-Ciklopropil-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-5-(pirolidin-1-ilmetil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(5-(Azetidin-1-ilmetil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Klor-4-[7-(5-((dimetilamino)metil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-{2-[5-Fluor-4-(7-{2-fluor-5-[(2-hidroksi-etilamino)metil]piridin-4-il}benzo[b]tiofen-2-il)pirimidin-2-ilamino]etil}imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-5-((propilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-(4-(7-(5-((Etilamino)metil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino)etil)imidazolidin-2-on,
1-{2-[4-(7-{5-[(Etil(metil)amino)metil]-2-fluorpiridin-4-il}benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino]etil}imidazolidin-2-on,
1-(2-{4-[7-(5-((Dietilamino)metil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(5-((Dimetilamino)metil)-2-fluorpiridin-4-il)-benzo[b]tiofen-2-il]-5-metilpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-5-((metilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(2-Fluor-5-((metilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]-5-metilpirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{5-Klor-4-[7-(2-fluor-5-((metilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-(2-{4-[7-(2-Fluor-5-((metilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)imidazolidin-2-on,
1-[2-(4-{7-[5-(1-Aminoetil)-2-fluorpiridin-4-il]benzo[b]tiofen-2-il}-5-fluorpirimidin-2-ilamino)etil]imidazolidin-2-on,
1-(2-{5-Fluor-4-[7-(2-fluor-5-((metilamino)metil)piridin-4-il)benzo[b]tiofen-2-il]pirimidin-2-ilamino}etil)-1H-imidazol-2(3H)-on,
1-{2-[5-Fluor-4-(7-{2-fluor-5-[(3,3,3-trifluorpropilamino)metil]piridin-4-il}benzo[b]tiofen-2-il)pirimidin-2-ilamino]etil}imidazolidin-2-on,
3-{[6-Fluor-4-(2-{5-fluor-2-[2-(2-oksoimidazolidin-1-il)etilamino]pirimidin-4-il}benzo[b]tiofen-7-il)piridin-3-il]metilamino}propanonitril,
1-(2-{4-[7-(5-(Aminometil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il]-5-fluorpirimidin-2-ilamino}etil)imidazolidin-2-on,
R-1-[2-(4-{7-[5-(1-Aminoetil)-2-fluorpiridin-4-il]benzo[b]tiofen-2-il}-5-fluorpirimidin-2-ilamino)etil]imidazolidin-2-on,
S-1-[2-(4-{7-[5-(1-Aminoetil)-2-fluorpiridin-4-il]benzo[b]tiofen-2-il}-5-fluorpirimidin-2-ilamino)etil]imidazolidin-2-on,
1-[2-(5-Fluor-4-{7-[2-fluor-5-(2-hidroksietoksi)piridin-4-il]benzo[b]tiofen-2-il}pirimidin-2-ilamino)etil]imidazolidin-2-on,
1-(2-(4-(7-(3-Etinilpiridin-4-il)benzo[b]tiofen-2-il)pirimidin-2-ilamino)etil)imidazolidin-2-on,
1-(2-(4-(7-(3-Etinilpiridin-4-il)benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino)etil)imidazolidin-2-on,
1-(2-(4-(7-(5-(1-Aminoetil)-2-klorpiridin-4-il)benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino)etil)imidazolidin-2-on,
S-1-(2-(4-(7-(5-(1-(Etilamino)etil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino)etil)imidazolidin-2-on,
R-1-(2-(4-(7-(5-(1-(Etilamino)etil)-2-fluorpiridin-4-il)benzo[b]tiofen-2-il)-5-fluorpirimidin-2-ilamino)etil)imidazolidin-2-on,
S-1-(2-(5-Fluor-4-(7-(2-fluor-5-(1-(metilamino)etil)piridin-4-il)benzo[b]tiofen-2-il)pirimidin-2-ilamino)etil)imidazolidin-2-on, i
R-1-(2-(5-Fluor-4-(7-(2-fluor-5-(1-(metilamino)etil)piridin-4-il)benzo[b]tiofen-2-il)pirimidin-2-ilamino)etil)imidazolidin-2-on;
ili njihove farmaceutski prihvatljive soli.
8. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s patentnim zahtjevima 1-7, ili njegova farmaceutski prihvatljiva sol, u kombinaciji s farmaceutski prihvatljivom podlogom, razrjeđivačem ili pomoćnom tvari.
9. Spoj u skladu s bilo kojim od patentnim zahtjeva 1-7, ili njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi u terapiji.
10. Spoj u skladu s bilo kojim od patentnim zahtjeva 1-7, ili njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi u liječenju raka, kojeg se bira iz skupine koju čine rak velikih stanica pluća, rak orofarinksa, rak jednjaka, rak želuca, melanom, epidermoidni karcinom kože, rak dojke, rak jajnika, karcinom endometrija, kolorektalni karcinom, neurogliom, glioblastom, karcinom štitnjače, rak vrata maternice, rak gušterače, rak prostate, hepatoblastom i ne-hodgkinski limfom kod sisavca.
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US87132206P | 2006-12-21 | 2006-12-21 | |
PCT/US2007/087046 WO2008076705A1 (en) | 2006-12-21 | 2007-12-11 | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer |
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JP (1) | JP2010513553A (hr) |
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EA (1) | EA016178B1 (hr) |
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TW200908981A (en) * | 2007-05-16 | 2009-03-01 | Lilly Co Eli | Triazolyl aminopyrimidine compounds |
EP2862861B1 (en) | 2012-06-14 | 2016-01-06 | Daiichi Sankyo Company, Limited | Piperidinylpyrazolopyridine derivative |
EP2929883A1 (en) | 2014-04-08 | 2015-10-14 | Institut Pasteur | Pyrazole derivatives as dihydroorotate dehydrogenase (DHODH) inhibitors |
KR20230142927A (ko) | 2022-04-04 | 2023-10-11 | 경희대학교 산학협력단 | 나프탈렌-2-일알킬기가 치환된 이미다졸리움 유도체 및 이를 유효성분으로 포함하는 암 치료용 조성물 |
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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 |
EP1831207B1 (en) | 2004-12-17 | 2012-11-14 | Amgen Inc. | Aminopyrimidine compounds as plk inhibitors |
TW200800201A (en) * | 2005-11-18 | 2008-01-01 | Lilly Co Eli | Pyrimidinyl benzothiophene compounds |
CN101437519A (zh) | 2006-03-31 | 2009-05-20 | 艾博特公司 | 吲唑化合物 |
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- 2007-12-11 CA CA002673564A patent/CA2673564A1/en not_active Abandoned
- 2007-12-11 PT PT07855060T patent/PT2125794E/pt unknown
- 2007-12-11 PL PL07855060T patent/PL2125794T3/pl unknown
- 2007-12-11 CN CN2007800477447A patent/CN101568539B/zh not_active Expired - Fee Related
- 2007-12-11 EA EA200970616A patent/EA016178B1/ru not_active IP Right Cessation
- 2007-12-11 RS RSP-2010/0547A patent/RS51526B/en unknown
- 2007-12-11 SI SI200730463T patent/SI2125794T1/sl unknown
- 2007-12-11 MX MX2009006635A patent/MX2009006635A/es active IP Right Grant
- 2007-12-11 BR BRPI0720607-0A2A patent/BRPI0720607A2/pt not_active IP Right Cessation
- 2007-12-11 AU AU2007334040A patent/AU2007334040B2/en not_active Ceased
- 2007-12-11 ES ES07855060T patent/ES2351371T3/es active Active
- 2007-12-11 DE DE602007010041T patent/DE602007010041D1/de active Active
- 2007-12-11 AT AT07855060T patent/ATE485291T1/de active
- 2007-12-11 EP EP07855060A patent/EP2125794B1/en active Active
- 2007-12-11 US US12/516,251 patent/US8063212B2/en not_active Expired - Fee Related
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- 2007-12-11 DK DK07855060.5T patent/DK2125794T3/da active
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- 2007-12-11 WO PCT/US2007/087046 patent/WO2008076705A1/en active Application Filing
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KR20090086111A (ko) | 2009-08-10 |
PT2125794E (pt) | 2011-01-10 |
EA200970616A1 (ru) | 2009-10-30 |
EP2125794B1 (en) | 2010-10-20 |
ES2351371T3 (es) | 2011-02-03 |
AU2007334040B2 (en) | 2012-02-16 |
RS51526B (en) | 2011-06-30 |
BRPI0720607A2 (pt) | 2014-04-08 |
DK2125794T3 (da) | 2011-01-24 |
SI2125794T1 (sl) | 2011-02-28 |
MX2009006635A (es) | 2009-06-30 |
KR101080594B1 (ko) | 2011-11-04 |
JP2010513553A (ja) | 2010-04-30 |
CY1110950T1 (el) | 2015-06-10 |
PL2125794T3 (pl) | 2011-04-29 |
AU2007334040A1 (en) | 2008-06-26 |
US20100081641A1 (en) | 2010-04-01 |
CA2673564A1 (en) | 2008-06-26 |
WO2008076705A1 (en) | 2008-06-26 |
EP2125794A1 (en) | 2009-12-02 |
US8063212B2 (en) | 2011-11-22 |
CN101568539A (zh) | 2009-10-28 |
DE602007010041D1 (de) | 2010-12-02 |
EA016178B1 (ru) | 2012-02-28 |
ATE485291T1 (de) | 2010-11-15 |
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