HRP20231614T1 - Spojevi pirolotriazina kao tam inhibitori - Google Patents
Spojevi pirolotriazina kao tam inhibitori Download PDFInfo
- Publication number
- HRP20231614T1 HRP20231614T1 HRP20231614TT HRP20231614T HRP20231614T1 HR P20231614 T1 HRP20231614 T1 HR P20231614T1 HR P20231614T T HRP20231614T T HR P20231614TT HR P20231614 T HRP20231614 T HR P20231614T HR P20231614 T1 HRP20231614 T1 HR P20231614T1
- Authority
- HR
- Croatia
- Prior art keywords
- phenyl
- amino
- carboxamide
- triazin
- pyrrolo
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title 1
- 150000003921 pyrrolotriazines Chemical class 0.000 title 1
- -1 aminosulfonylamino Chemical group 0.000 claims 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 33
- 125000001424 substituent group Chemical group 0.000 claims 33
- 150000001875 compounds Chemical class 0.000 claims 28
- 150000003839 salts Chemical class 0.000 claims 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 24
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims 23
- 229910020008 S(O) Inorganic materials 0.000 claims 22
- 125000000217 alkyl group Chemical group 0.000 claims 22
- 125000002947 alkylene group Chemical group 0.000 claims 21
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 20
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 16
- 229910052736 halogen Inorganic materials 0.000 claims 14
- 150000002367 halogens Chemical class 0.000 claims 14
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 13
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 11
- 229910052799 carbon Inorganic materials 0.000 claims 11
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims 11
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 9
- 101100005620 Caenorhabditis elegans cyb-3 gene Proteins 0.000 claims 8
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 7
- 229910052717 sulfur Inorganic materials 0.000 claims 7
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims 6
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 6
- 125000004432 carbon atom Chemical group C* 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 239000003937 drug carrier Substances 0.000 claims 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 4
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 4
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 4
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 4
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims 4
- ZYCWFLSNKRWWQH-UHFFFAOYSA-N N-[4-[4-amino-7-(4-hydroxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCC(CC1)O)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O ZYCWFLSNKRWWQH-UHFFFAOYSA-N 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 4
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 125000003386 piperidinyl group Chemical group 0.000 claims 4
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 4
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 3
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 3
- 101100059439 Caenorhabditis elegans cyb-1 gene Proteins 0.000 claims 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
- 125000005842 heteroatom Chemical group 0.000 claims 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 101100273638 Caenorhabditis elegans cya-1 gene Proteins 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- MVFGYMXGYJXEFF-UHFFFAOYSA-N N-[4-(4-amino-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCNCC1)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F MVFGYMXGYJXEFF-UHFFFAOYSA-N 0.000 claims 2
- ONSJKYVPJNEILC-UHFFFAOYSA-N N-[4-[4-amino-7-(4-hydroxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCC(CC1)O)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F ONSJKYVPJNEILC-UHFFFAOYSA-N 0.000 claims 2
- YTGKQQWXYQLBGX-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F YTGKQQWXYQLBGX-UHFFFAOYSA-N 0.000 claims 2
- UVHZFGWSWUQZFX-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCOC)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F UVHZFGWSWUQZFX-UHFFFAOYSA-N 0.000 claims 2
- CLKZYSCOSIBANL-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(dimethylcarbamoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)N(C)C)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F CLKZYSCOSIBANL-UHFFFAOYSA-N 0.000 claims 2
- DUXXBRYGDLQJQM-UHFFFAOYSA-N N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)N(C)CC)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=2CCCC(C=2C=1)=O)C1=CC=C(C=C1)F)=O)F DUXXBRYGDLQJQM-UHFFFAOYSA-N 0.000 claims 2
- HSXPKDPRRLEBQG-UHFFFAOYSA-N N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)N(C)CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=2CCCC(C=2C=1)=O)C1=CC=C(C=C1)F)=O HSXPKDPRRLEBQG-UHFFFAOYSA-N 0.000 claims 2
- ZMODBJGIKIUPSW-UHFFFAOYSA-N N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)N(C)CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O ZMODBJGIKIUPSW-UHFFFAOYSA-N 0.000 claims 2
- PLCVJNJRUVNDEY-UHFFFAOYSA-N N-[4-[7-(1-acetylpiperidin-4-yl)-4-aminopyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound C(C)(=O)N1CCC(CC1)C1=CC(=C2C(=NC=NN21)N)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F PLCVJNJRUVNDEY-UHFFFAOYSA-N 0.000 claims 2
- QRYMEHUICLZZCD-UHFFFAOYSA-N N-[4-[7-(1-acetylpiperidin-4-yl)-4-aminopyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound C(C)(=O)N1CCC(CC1)C1=CC(=C2C(=NC=NN21)N)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F QRYMEHUICLZZCD-UHFFFAOYSA-N 0.000 claims 2
- 108091000080 Phosphotransferase Proteins 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 201000010536 head and neck cancer Diseases 0.000 claims 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 102000020233 phosphotransferase Human genes 0.000 claims 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- ZXNZHVDQMZJUKH-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound O=C1C(C(=O)N)=CC=CN1C1=CC=C(F)C=C1 ZXNZHVDQMZJUKH-UHFFFAOYSA-N 0.000 claims 1
- CDYZISGCDITLOI-UHFFFAOYSA-N 4-amino-5-[4-[[3-(3-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carbonyl]amino]phenyl]-N,N-dimethylpyrrolo[2,1-f][1,2,4]triazine-7-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C(=O)N(C)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1=CC(=CC=C1)F)=O CDYZISGCDITLOI-UHFFFAOYSA-N 0.000 claims 1
- NFCXQIHBUDNOQY-UHFFFAOYSA-N 5-N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-methyl-6-oxo-1-phenylpyridine-3,5-dicarboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(=C(C=1)C(=O)N)C)C1=CC=CC=C1)=O NFCXQIHBUDNOQY-UHFFFAOYSA-N 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 claims 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims 1
- 201000003076 Angiosarcoma Diseases 0.000 claims 1
- 208000003950 B-cell lymphoma Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000011691 Burkitt lymphomas Diseases 0.000 claims 1
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 1
- 101100310926 Caenorhabditis elegans sra-3 gene Proteins 0.000 claims 1
- 101100310927 Caenorhabditis elegans sra-4 gene Proteins 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 208000005243 Chondrosarcoma Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 102100038417 Cytoplasmic FMR1-interacting protein 1 Human genes 0.000 claims 1
- 101710181791 Cytoplasmic FMR1-interacting protein 1 Proteins 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
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 1
- 201000008808 Fibrosarcoma Diseases 0.000 claims 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 1
- 208000001258 Hemangiosarcoma Diseases 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010024612 Lipoma Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
- SDLQPJGQEFSRRE-UHFFFAOYSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F SDLQPJGQEFSRRE-UHFFFAOYSA-N 0.000 claims 1
- DLOQHHJANJFFJT-UHFFFAOYSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=2CCCC(C=2C=1)=O)C1=CC=C(C=C1)F)=O DLOQHHJANJFFJT-UHFFFAOYSA-N 0.000 claims 1
- WDUZHMCHWHGCJJ-DEOSSOPVSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-[(1R)-2-hydroxy-1-phenylethyl]-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)[C@@H](CO)C1=CC=CC=C1)=O WDUZHMCHWHGCJJ-DEOSSOPVSA-N 0.000 claims 1
- SXNWEPPMFXZDBN-GOSISDBHSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-[(2R)-1-hydroxybutan-2-yl]-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)[C@H](CC)CO)=O SXNWEPPMFXZDBN-GOSISDBHSA-N 0.000 claims 1
- ASXZIOFDDZWNBH-CQSZACIVSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-[(2R)-1-hydroxypropan-2-yl]-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)[C@@H](CO)C)=O ASXZIOFDDZWNBH-CQSZACIVSA-N 0.000 claims 1
- YOGPBAXHXFDATQ-UHFFFAOYSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-benzyl-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)CC1=CC=CC=C1)=O YOGPBAXHXFDATQ-UHFFFAOYSA-N 0.000 claims 1
- XLRSOQOKZYHHPE-UHFFFAOYSA-N N-[4-(4-amino-7-ethylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-methyl-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2CC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C)=O XLRSOQOKZYHHPE-UHFFFAOYSA-N 0.000 claims 1
- SSNOOYVRHMFBIF-UHFFFAOYSA-N N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O)F SSNOOYVRHMFBIF-UHFFFAOYSA-N 0.000 claims 1
- UJBDZOICZAPMEZ-UHFFFAOYSA-N N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F UJBDZOICZAPMEZ-UHFFFAOYSA-N 0.000 claims 1
- WDSAVECIVQHDAD-UHFFFAOYSA-N N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O WDSAVECIVQHDAD-UHFFFAOYSA-N 0.000 claims 1
- GTZDUBKNXPYACI-UHFFFAOYSA-N N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O GTZDUBKNXPYACI-UHFFFAOYSA-N 0.000 claims 1
- BHGAULURFLXYMT-UHFFFAOYSA-N N-[4-(4-amino-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCNCC1)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F BHGAULURFLXYMT-UHFFFAOYSA-N 0.000 claims 1
- ZPVSNCIOAMEWBR-UHFFFAOYSA-N N-[4-(4-amino-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCNCC1)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O ZPVSNCIOAMEWBR-UHFFFAOYSA-N 0.000 claims 1
- FFCKHBSETQPNFE-UHFFFAOYSA-N N-[4-(4-amino-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCNCC1)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O FFCKHBSETQPNFE-UHFFFAOYSA-N 0.000 claims 1
- NPMHPYDYYNJHLT-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O NPMHPYDYYNJHLT-UHFFFAOYSA-N 0.000 claims 1
- CDLLABUAFGKJDH-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O CDLLABUAFGKJDH-UHFFFAOYSA-N 0.000 claims 1
- MFXKIWDPRIHODU-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-2-oxo-1-phenyl-5-pyrimidin-2-ylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C(=C(C=1)C1=NC=CC=N1)C)C1=CC=CC=C1)=O MFXKIWDPRIHODU-UHFFFAOYSA-N 0.000 claims 1
- LFZTUWMBFUXEBV-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylsulfonylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)S(=O)(=O)C)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F LFZTUWMBFUXEBV-UHFFFAOYSA-N 0.000 claims 1
- GTYUKUURXPBNLQ-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylsulfonylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)S(=O)(=O)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O GTYUKUURXPBNLQ-UHFFFAOYSA-N 0.000 claims 1
- UKJAACLEQSSYIE-UHFFFAOYSA-N N-[4-[4-amino-7-(1-methylsulfonylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)S(=O)(=O)C)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O UKJAACLEQSSYIE-UHFFFAOYSA-N 0.000 claims 1
- OXPQSGRKFNVPAM-UHFFFAOYSA-N N-[4-[4-amino-7-(4-cyanocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound Nc1ncnn2c(cc(-c3ccc(NC(=O)c4cccn(-c5ccc(F)cc5)c4=O)cc3F)c12)C1CCC(CC1)C#N OXPQSGRKFNVPAM-UHFFFAOYSA-N 0.000 claims 1
- PHPKMXFRPJBGSR-UHFFFAOYSA-N N-[4-[4-amino-7-(4-cyanocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound Nc1ncnn2c(cc(-c3ccc(NC(=O)c4cccn(-c5ccccc5)c4=O)cc3F)c12)C1CCC(CC1)C#N PHPKMXFRPJBGSR-UHFFFAOYSA-N 0.000 claims 1
- HVMCHMJVEKCRCI-UHFFFAOYSA-N N-[4-[4-amino-7-(4-cyanocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound Nc1ncnn2c(cc(-c3ccc(NC(=O)c4cccn(-c5ccc(F)cc5)c4=O)cc3)c12)C1CCC(CC1)C#N HVMCHMJVEKCRCI-UHFFFAOYSA-N 0.000 claims 1
- KZRUTRKOHDQVNC-UHFFFAOYSA-N N-[4-[4-amino-7-(4-cyanocyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCC(CC1)C#N)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O KZRUTRKOHDQVNC-UHFFFAOYSA-N 0.000 claims 1
- NSGSTMADVSYLQK-UHFFFAOYSA-N N-[4-[4-amino-7-(4-hydroxycyclohexyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCC(CC1)O)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O NSGSTMADVSYLQK-UHFFFAOYSA-N 0.000 claims 1
- LLWJULPMRBZXBX-UHFFFAOYSA-N N-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCOCC1)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F LLWJULPMRBZXBX-UHFFFAOYSA-N 0.000 claims 1
- WRADGJQBDXJRIT-UHFFFAOYSA-N N-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCOCC1)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O WRADGJQBDXJRIT-UHFFFAOYSA-N 0.000 claims 1
- GPNOEUDRIWKLGC-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=2CCCC(C=2C=1)=O)C1=CC=C(C=C1)F)=O)F GPNOEUDRIWKLGC-UHFFFAOYSA-N 0.000 claims 1
- ZDLYCRBETASLAJ-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F ZDLYCRBETASLAJ-UHFFFAOYSA-N 0.000 claims 1
- NNTAENHFVLQVTG-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=CC=C(C=C1)NC(=O)C=1C(N(C=2CCCC(C=2C=1)=O)C1=CC=C(C=C1)F)=O NNTAENHFVLQVTG-UHFFFAOYSA-N 0.000 claims 1
- WDXBRUHVKWGDOP-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O WDXBRUHVKWGDOP-UHFFFAOYSA-N 0.000 claims 1
- DGOGREBGMZWKCT-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCO)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O DGOGREBGMZWKCT-UHFFFAOYSA-N 0.000 claims 1
- AWMRXNYJPYBABO-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCOC)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F AWMRXNYJPYBABO-UHFFFAOYSA-N 0.000 claims 1
- QEPUHXTUGSVGOF-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCOC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=C(C=C1)F)=O QEPUHXTUGSVGOF-UHFFFAOYSA-N 0.000 claims 1
- KQVZUBPWFJXMKN-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)CCOC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O KQVZUBPWFJXMKN-UHFFFAOYSA-N 0.000 claims 1
- PNOYDYDKHRZGJD-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(5-fluoropyridin-3-yl)-5,6-dimethyl-2-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(=C(C=1)C)C)C=1C=NC=C(C=1)F)=O PNOYDYDKHRZGJD-UHFFFAOYSA-N 0.000 claims 1
- RTQKZBQTKQUQFE-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(5-fluoropyridin-3-yl)-6-methyl-2-oxo-5-(1,3-thiazol-4-yl)pyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(=C(C=1)C=1N=CSC=1)C)C=1C=NC=C(C=1)F)=O RTQKZBQTKQUQFE-UHFFFAOYSA-N 0.000 claims 1
- INCLUHXJYYFKBR-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-cyclopropyl-2,4-dioxo-3-phenylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C1CC1)=O)C1=CC=CC=C1)=O INCLUHXJYYFKBR-UHFFFAOYSA-N 0.000 claims 1
- LMVTWQWJLDGLDK-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-cyclopropyl-2,4-dioxo-3-pyridin-3-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C1CC1)=O)C=1C=NC=CC=1)=O LMVTWQWJLDGLDK-UHFFFAOYSA-N 0.000 claims 1
- HPMRGEUXGIDRHY-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-cyclopropyl-6-methyl-4-oxo-5-pyridin-2-ylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(C(=C(N(C=1)C1CC1)C)C1=NC=CC=C1)=O HPMRGEUXGIDRHY-UHFFFAOYSA-N 0.000 claims 1
- ICWGNNCQWSWBRG-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-cyclopropyl-6-methyl-5-(1,3-oxazol-2-yl)-4-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C1=CN(C(=C(C1=O)C=1OC=CN=1)C)C1CC1 ICWGNNCQWSWBRG-UHFFFAOYSA-N 0.000 claims 1
- CSINNIKEQPTXBQ-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-cyclopropyl-6-methyl-5-(2-methylpyridin-3-yl)-4-oxopyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(C(=C(N(C=1)C1CC1)C)C=1C(=NC=CC=1)C)=O CSINNIKEQPTXBQ-UHFFFAOYSA-N 0.000 claims 1
- YBXWUVFZDRSTIV-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenyl-6-pyridin-2-ylpyridine-3-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C1=CC=C(N(C1=O)C1=CC=CC=C1)C1=NC=CC=C1 YBXWUVFZDRSTIV-UHFFFAOYSA-N 0.000 claims 1
- FAPRLJWBIKQLPC-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(1,4-dimethylpyrazol-3-yl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1=NN(C=C1C)C)=O FAPRLJWBIKQLPC-UHFFFAOYSA-N 0.000 claims 1
- HKOWJECZABVSBF-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(1-methylpyrazol-3-yl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1=NN(C=C1)C)=O HKOWJECZABVSBF-UHFFFAOYSA-N 0.000 claims 1
- IMHPXAIWFQNXKF-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(1-methylpyrazol-4-yl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C=1C=NN(C=1)C)=O IMHPXAIWFQNXKF-UHFFFAOYSA-N 0.000 claims 1
- NSTWZAWVSNQWFD-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(3-cyanophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1=CC(=CC=C1)C#N)=O NSTWZAWVSNQWFD-UHFFFAOYSA-N 0.000 claims 1
- SBCZVXIAPCZORV-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(5-methyl-1,2-oxazol-3-yl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1=NOC(=C1)C)=O SBCZVXIAPCZORV-UHFFFAOYSA-N 0.000 claims 1
- VRBCYHMHHGOSNK-UHFFFAOYSA-N N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-cyclohexyl-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(C(C)C)=O)C1=CC=C(C=C1)NC(=O)C=1C(N(C(N(C=1)C(C)C)=O)C1CCCCC1)=O VRBCYHMHHGOSNK-UHFFFAOYSA-N 0.000 claims 1
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- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- WHJOYBCBROPEDL-UHFFFAOYSA-N methyl 4-[4-amino-5-[2-fluoro-4-[(2-oxo-1-phenylpyridine-3-carbonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidine-1-carboxylate Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)OC)C1=C(C=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O)F WHJOYBCBROPEDL-UHFFFAOYSA-N 0.000 claims 1
- LLGTZIXASKDKRV-UHFFFAOYSA-N methyl 4-[4-amino-5-[4-[(2-oxo-1-phenylpyridine-3-carbonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidine-1-carboxylate Chemical compound NC1=NC=NN2C1=C(C=C2C1CCN(CC1)C(=O)OC)C1=CC=C(C=C1)NC(=O)C=1C(N(C=CC=1)C1=CC=CC=C1)=O LLGTZIXASKDKRV-UHFFFAOYSA-N 0.000 claims 1
- 208000009091 myxoma Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D403/14—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 three or more hetero rings
Claims (27)
1. Spoj, naznačen time, da je predstavljen Formulom (IIb1) ili Formulom (IIb2):
[image]
ili njegova farmaceutski prihvatljiva sol, gdje:
R1 je A1-A2-A3-RA;
A1 se bira od sljedećih: veza, CyA1, -Y-, -C1-3 alkilen-, -C1-3 alkilen-Y-, -Y-C1-3 alkilen-, i -C1-2 alkilen-Y-C1-2 alkilen-; pri čemu je svaka alkilen skupina opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, CN, OH, C1-3 alkil, C1-3 alkoksi, C1-3 haloalkil, C1-3 haloalkoksi, amino, C1-3 alkilamino, i di(C1-3 alkil)amino;
A2 se bira od sljedećih: veza, CyA2, -Y-, -C1-3 alkilen-, -C1-3 alkilen-Y-, -Y-C1-3 alkilen-, i -C1-2 alkilen-Y-C1-2 alkilen-; pri čemu je svaka alkilen skupina opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, CN, OH, C1-3 alkil, C1-3 alkoksi, C1-3 haloalkil, C1-3 haloalkoksi, amino, C1-3 alkilamino, i di(C1-3 alkil)amino;
A3 se bira od sljedećih: veza, CyA3, -Y-, -C1-3 alkilen-, -C1-3 alkilen-Y-, -Y-C1-3 alkilen-, i -C1-2 alkilen-Y-C1-2 alkilen-; pri čemu je svaka alkilen skupina opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, CN, OH, C1-3 alkil, C1-3 alkoksi, C1-3 haloalkil, C1-3 haloalkoksi, amino, C1-3 alkilamino, i di(C1-3 alkil)amino;
RA je H,C1-6 alkil, C1-6 haloalkil, halogen, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1ORd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, ili S(O)2NRc1Rd1; pri čemu je spomenuti C1-6 alkil, ili C1-6 haloalkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R11;
Y je O, S, S(O), S(O)2, C(O), C(O)NRf, NRfC(O), NRfC(O)NRf, NRfS(O)2NRf, S(O)2NRf, NRfS(O)2, ili NRf;
svaki Rf se neovisno bira od H i C1-3 alkila;
CyA1 je C3-7 cikloalkil, fenil, 5-6-člani heteroaril, ili 4-7-člani heterocikloalkil; pri čemu svaki od 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, ima najmanje jedan atom ugljika koji tvori prsten i 1, 2, 3 ili 4 heteroatoma koji tvore prsten, neovisno odabrana od N, O i S; dok se N i S opcionalno oksidiraju; pri čemu je atom ugljika koji tvori prsten od C3-7 cikloalkila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s okso u svrhu tvorbe karbonilne skupine; i pri čemu je svaki od C3-7 cikloalkila, fenila, 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od RA1;
svaki RA1 se neovisno bira od sljedećih: OH, NO2, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, cijano-C1-3 alkil, HO-C1-3 alkil, H2N-C1-3 alkil, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, C1-6 alkilkarbonilamino, C1-6 alkilsulfonilamino, aminosulfonil, C1-6 alkilaminosulfonil, di(C1-6 alkil)aminosulfonil, aminosulfonilamino, C1-6 alkilaminosulfonilamino, di(C1-6 alkil)aminosulfonilamino, aminokarbonilamino, C1-6 alkilaminokarbonilamino, i di(C1-6 alkil)aminokarbonilamino;
CyA2 je C3-7 cikloalkil, fenil, 5-6-člani heteroaril, ili 4-7-člani heterocikloalkil; pri čemu svaki od 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, ima najmanje jedan atom ugljika koji tvori prsten i 1, 2, 3 ili 4 heteroatoma koji tvore prsten, neovisno odabrana od N, O i S; dok se N i S opcionalno oksidiraju; pri čemu je atom ugljika koji tvori prsten od C3-7 cikloalkila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s okso u svrhu tvorbe karbonilne skupine; i pri čemu je svaki od C3-7 cikloalkila, fenila, 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od RA2;
svaki RA2 se neovisno bira od sljedećih: OH, NO2, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, cijano-C1-3 alkil, HO-C1-3 alkil, H2N-C1-3 alkil, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, C1-6 alkilkarbonilamino, C1-6 alkilsulfonilamino, aminosulfonil, C1-6 alkilaminosulfonil, di(C1-6 alkil)aminosulfonil, aminosulfonilamino, C1-6 alkilaminosulfonilamino, di(C1-6 alkil)aminosulfonilamino, aminokarbonilamino, C1-6 alkilaminokarbonilamino, i di(C1-6 alkil)aminokarbonilamino;
CyA3 je C3-7 cikloalkil, fenil, 5-6-člani heteroaril, ili 4-7-člani heterocikloalkil; pri čemu svaki od 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, ima najmanje jedan atom ugljika koji tvori prsten i 1, 2, 3 ili 4 heteroatoma koji tvore prsten, neovisno odabrana od N, O i S; dok se N i S opcionalno oksidiraju; pri čemu je atom ugljika koji tvori prsten od C3-7 cikloalkila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s okso u svrhu tvorbe karbonilne skupine; i pri čemu je svaki od C3-7 cikloalkila, fenila, 5-6-članog heteroarila, i 4-7-članog heterocikloalkila, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od RA3;
svaki RA3 se neovisno bira od sljedećih: OH, NO2, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, cijano-C1-3 alkil, HO-C1-3 alkil, H2N-C1-3 alkil, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, C1-6 alkilkarbonilamino, C1-6 alkilsulfonilamino, aminosulfonil, C1-6 alkilaminosulfonil, di(C1-6 alkil)aminosulfonil, aminosulfonilamino, C1-6 alkilaminosulfonilamino, di(C1-6 alkil)aminosulfonilamino, aminokarbonilamino, C1-6 alkilaminokarbonilamino, i di(C1-6 alkil)aminokarbonilamino;
svaki RC se neovisno bira od sljedećih: OH, CN, halogen, C1-4 alkil, C1-3 haloalkil, C1-4 alkoksi, C1-3 haloalkoksi, cijano-C1-3 alkil, HO-C1-3 alkil, amino, C1-4 alkilamino, di(C1-4 alkil)amino, C1-4 alkilsulfinil, C1-4 alkilsulfonil, karbamil, C1-4 alkilkarbamil, di(C1-4 alkil)karbamil, karboksi, C1-4 alkilkarbonil, C1-4 alkoksikarbonil, C1-4 alkilkarbonilamino, C1-4 alkilsulfonilamino, aminosulfonil, C1-4 alkilaminosulfonil, i di(C1-4 alkil)aminosulfonil;
CyB je
[image]
pri čemu je svaki od CyB-1, CyB-2, CyB-3, i CyB-10, opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od RB;
svaki RB se neovisno bira od sljedećih: halogen, C1-6 alkil, C2-6 alkinil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(O)Rb2, i NRc2C(O)ORa2; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkinil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R12;
svaki R11 se neovisno bira od sljedećih: CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3ORd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
svaki R12 se neovisno bira od sljedećih: halogen, CN, NO2, C1-6 alkil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4ORd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, i S(O)2NRc4Rd4;
pri čemu je svaki spomenuti C1-6 alkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg;
svaki od Ra1, Rc1, i Rd1 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; gdje je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg; ili
alternativno, Rc1 i Rd1 koji su vezani s istim N atomom, zajedno s N atomom s kojim su vezani, tvore 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od Rg;
Rb1 se bira od C1-6 alkila, i C1-6 haloalkila, od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg;
Re1 se bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6 alkiltio, C1-6 alkilsulfonil, C1-6 alkilkarbonil, C1-6 alkilaminosulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, aminosulfonil, C1-6 alkilaminosulfonil, i di(C1-6 alkil)aminosulfonil;
svaki od Ra2, Rc2, i Rd2 se neovisno bira od sljedećih: H, C1-6 alkil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil; gdje je svaki spomenuti C1-6 alkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R12; ili
alternativno, bilo koji od Rc2 i Rd2 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvore 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od R12;
svaki Rb2 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil; od kojih je svaki spomenuti opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R12;
svaki od Ra3, Rc3, i Rd3 se neovisno bira od sljedećih: H, C1-6 alkil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, C3-6 cikloalkil-C1-4 alkilen, fenil-C1-4 alkilen, 5-6-člani heteroaril-C1-4 alkilen, i 4-7-člani heterocikloalkil-C1-4 alkilen; gdje je svaki spomenuti C1-6 alkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, C3-6 cikloalkil-C1-4 alkilen, fenil-C1-4 alkilen, 5-6-člani heteroaril-C1-4 alkilen, i 4-7-člani heterocikloalkil-C1-4 alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg; ili
alternativno, bilo koji od Rc3 i Rd3 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvore 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od Rg;
svaki Rb3 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, C3-6 cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, C3-6 cikloalkil-C1-4 alkilen, fenil-C1-4 alkilen, 5-6-člani heteroaril-C1-4 alkilen, i 4-7-člani heterocikloalkil-C1-4 alkilen, od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg;
svaki od Ra4, Rc4, i Rd4 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; pri čemu je spomenuti C1-6 alkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg; ili
alternativno, bilo koji od Rc4 i Rd4 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvore 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od Rg;
svaki Rb4 se neovisno bira od sljedećih: C1-6 alkil, i C1-6 haloalkil, od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od Rg;
svaki Rg se neovisno bira od sljedećih: OH, NO2, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, cijano-C1-3 alkil, HO-C1-3 alkil, H2N-C1-3 alkil, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, C1-6 alkilkarbonilamino, C1-6 alkilsulfonilamino, aminosulfonil, C1-6 alkilaminosulfonil, di(C1-6 alkil)aminosulfonil, aminosulfonilamino, C1-6 alkilaminosulfonilamino, di(C1-6 alkil)aminosulfonilamino, aminokarbonilamino, C1-6 alkilaminokarbonilamino, i di(C1-6 alkil)aminokarbonilamino;
i
gdje se „cikloalkil“ odnosi na nearomatske cikličke hidrokarbone uključujući ciklirane alkil i/ili alkenil skupine,
uključujući ostatke skupina koji imaju jedan ili više aromatskih prstenova spojenih na cikloalkilni prsten;
uz uvjet da:
1) A1-A2-A3 nije Y-Y kada je jedan od A1, A2 ili A3 veza, ili Y-Y-Y; i
2) kada A3 je -Y- ili -C1-3alkilen-Y-, tada RA je H, C1-6alkil, ili C1-6 haloalkil, pri čemu je spomenuti C1-6alkil, ili C1-6haloalkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R11.
2. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) R1 je H, halogen, C1-6 alkil, ili C1-6 haloalkil; ili
(b) R1 je C1-6 alkil; ili
(c) R1 je A2-A3-RA; ili
(d) R1 je CyA3-RA.
3. Spoj prema bilo kojem od patentnih zahtjeva 1, 2(c), i 2(d), ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) CyA3 je C3-7 cikloalkil, 5-6-člani heteroaril, ili 4-7-člani heterocikloalkil; od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od RA3; ili
(b) CyA3 je C3-6 cikloalkil, ili 4-6-člani heterocikloalkil; od kojih je svaki opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od RA3; ili
(c) CyA3 je piperidinil, cikloheksil, tetrahidropiranil, pirazolil, piridinil, azetidinil, ciklopropil, ili morfolinil; od kojih je svaki opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od RA3; ili
(d) CyA3 je piperidinil, cikloheksil, ili tetrahidropiranil; od kojih je svaki opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od RA3; ili
(e) CyA3 je
[image]
gdje je svaki od CyA3-1, CyA3-2, i CyA3-3, opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od RA3.
4. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) R1 se bira od metila, etila,
[image]
ili
(b) R1 je
[image]
ili
(c) R1je
[image]
5. Spoj prema bilo kojem od patentnih zahtjeva 1, 2(c), i 2(d), ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) RA je C1-6 alkil, CN, ORa1, NRc1Rd1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, ili S(O)2NRc1Rd1; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od R11, uz uvjet da ako je RA vezan s atomom dušika, tada RA nije CN, ORa1, ili NRc1Rd1; ili
(b) RA je C1-6 alkil, CN, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, i S(O)2Rb1; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1 supstituentom neovisno odabranim od R11, uz uvjet da ako je RA vezan s atomom dušika, tada RA nije CN, ili ORa1.
6. Spoj prema bilo kojem od patentnih zahtjeva 1-5, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) svaki R11 je neovisno ORa3; ili
(b) svaki R11 je neovisno OH ili OCH3.
7. Spoj prema bilo kojem od patentnih zahtjeva 1, 2(c), 2(d), 5, i 6, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) CyA3 je piperidinil, cikloheksil, tetrahidropiranil, pirazolil, piridinil, azetidinil, ciklopropil, ili morfolinil; od kojih je svaki opcionalno supstituiran s RA koji se neovisno bira od sljedećih: CH3, CN, OH, CH2CH2OH, CH2CH2OCH3, C(O)CH3, C(O)CH2CH3, C(O)CH(CH3)2, C(O)CH2OH, C(O)CH(CH3)OH, S(O)2CH3, C(O)OCH3, C(O)N(CH3)2, C(O)NH(CH3), C(O)N(CH2CH3)2, C(O)NH(CH2CH3), C(O)N(CH3)(CH2CH3), CH2C(O)N(CH3)2, 1-metil-2-oksopirolidin-3-il, C(O)(ciklopropil), N(CH3)2, i C(O)(morfolin-4-il); ili
(b) CyA3 je piperidinil, cikloheksil, ili tetrahidropiranil; od kojih je svaki opcionalno supstituiran s RA koji se neovisno bira od sljedećih: CH3, CN, OH, CH2CH2OH, CH2CH2OCH3, C(O)CH3, C(O)CH2CH3, C(O)CH(CH3)2, C(O)CH2OH, C(O)CH(CH3)OH, S(O)2CH3, C(O)OCH3, C(O)N(CH3)2, C(O)NH(CH3), C(O)N(CH2CH3)2, C(O)NH(CH2CH3), C(O)N(CH3)(CH2CH3), i C(O)(morfolin-4-il).
8. Spoj prema bilo kojem od patentnih zahtjeva 1-7, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) svaki RB je neovisno nesupstituirani fenil, 4-fluoro-fenil, 3-fluorofenil, 2-fluorofenil, CH2(fenil), CH(CH2OH)fenil, Br, Cl, CN, CH3, CHF2, CH2CH3, CH2OCH3, CH2OCH2CH3, CH(CH3)2, CH(CH2OH)CH2CH3, CH(CH2OH)CH3, CH2CH2OH, CH2CH(OH)(CH3), OCH3, OCH2CH3, C(O)NH2, C(O)CH3, 2,5-difluorofenil, 3-piridinil, 2-piridinil, 1-metil-1H-pirazol-4-il, 1-metil-1H-pirazol-3-il, 1-metil-1H-pirazol-5-il, 1,4-dimetil-1H-pirazol-3-il, 1,5-dimetil-1H-pirazol-3-il, 2-metiltiazol-5-il, cikloheksil, 3-cijanofenil, 5-metilizoksazol-3-il, 5-fluoropiridin-3-il, 5-fluoropiridin-2-il, 3-cijanofenil, CH2CN, tiazol-4-il, 6-metilpiridin-3-il, 2-metilpiridin-3-il, 6-metilpiridin-2-il, pirimidin-2-il, morfolin-4-il, ciklopropil, oksazol-2-il, CCCH(OH)(CH3), ili C(O)NH(4-fluoro-fenil); ili
(b) svaki RB je neovisno nesupstituirani fenil, 4-fluoro-fenil, 3-fluorofenil, 2-fluorofenil, 2-piridinil, CH2(fenil), CH(CH2OH)fenil, CH3, CH2CH3, CH(CH3)2, CH(CH2OH)CH2CH3, CH(CH2OH)CH3, CH2CH2OH, OCH3, OCH2CH3, ili C(O)NH(4-fluoro-fenil).
9. Spoj prema bilo kojem od patentnih zahtjeva 1-7, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) CyB je
[image]
pri čemu je svaki od CyB-1, CyB-2, CyB-3, i CyB-10 opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od RB;
svaki RB je neovisno metil, etil, izopropil, sek-butil, 2-piridinil, ili fenil, od kojih je svaki opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od R12;
svaki R12 se neovisno bira od C1-6 alkila, halogena, fenila, i ORa4;
pri čemu je svaki od C1-6 alkila i fenila opcionalno supstituiran s 1 ili 2 supstituenta neovisno odabrana od Rg skupine;
svaki Ra4 je H ili C1-3 alkil; i
svaki Rg se neovisno bira od halogena; ili
(b) CyB je
[image]
gdje je svaki od CyB-1, CyB-2, i CyB-3, opcionalno supstituiran s 1, 2 ili 3 skupine neovisno odabrane od sljedećih: nesupstituirani fenil, 4-fluoro-fenil, 3-fluorofenil, 2-fluorofenil, 2-piridinil, CH2(fenil), CH(CH2OH)fenil, CH3, CH2CH3, CH(CH3)2, CH(CH2OH)CH2CH3, CH(CH2OH)CH3, CH2CH2OH, OCH2CH3, i OCH3; ili
(c) CyB je
[image]
gdje je svaki od CyB-2 i CyB-3 opcionalno supstituiran s 1, 2 ili 3 skupine koje se neovisno biraju od nesupstituiranog fenila, CH(CH3)2, i 2-piridinila.
10. Spoj prema bilo kojem od patentnih zahtjeva 1-9, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(a) svaki RC je neovisno F, Cl, ili metil; ili
(b) svaki RC je F.
11. Spoj prema patentnom zahtjevu 1, naznačen time, da je predstavljen Formulom (IIg1) ili Formulom (IIg2):
[image]
ili njegova farmaceutski prihvatljiva sol.
12. Spoj prema patentnom zahtjevu 1, naznačen time, da:
(a) spoj se bira od sljedećih:
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-[(1R)-2-hidroksi-1-feniletil]-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-[(1R)-2-hidroksi-1-metiletil]-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-[(1R)-1-(hidroksimetil)propil]-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-benzil-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-metil-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-metilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-metilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-metilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-metilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-etilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(tetrahidro-2H-piran-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(tetrahidro-2H-piran-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-1-(4-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(tetrahidro-2H-piran-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(tetrahidro-2H-piran-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-
1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-metilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-metilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-4-[4-amino-7-(1-metilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-metilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]fenil}-
2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]fenil}-
1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-
3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(cis-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-cijanocikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-
3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-piperidin-4-ilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-piperidin-4-ilpirolo[2,1-f][1,2,4]triazin-5-il)fenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-piperidin-4-ilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-
2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-piperidin-4-ilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-
1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
metil 4-[4-amino-5-(4-{[(2-okso-1-fenil-1,2-dihidropiridin-3-il)karbonil]
amino}fenil)pirolo[2,1-f][1,2,4]triazin-7-il]piperidin-1-karboksilat;
metil 4-{4-amino-5-[4-({[1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-il)karbonil}amino)fenil]pirolo[2,1-f][1,2,4]triazin-7-il}piperidin-1-karboksilat;
metil 4-[4-amino-5-(2-fluoro-4-{[(2-okso-1-fenil-1,2-dihidropiridin-3-il)karbonil]amino}fenil)pirolo[2,1-f][1,2,4]triazin-7-il]piperidin-1-karboksilat;
metil 4-[4-amino-5-[2-fluoro-4-({[1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-il]karbonil}amino)fenil]pirolo[2,1-f][1,2,4]triazin-7-il}piperidin-1-karboksilat;
N-(4-{4-amino-7-[1-(metilsulfonil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(metilsulfonil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(metilsulfonil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(metilsulfonil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-{1-[(dimetilamino)karbonil]piperidin-4-il}pirolo[2,1-f]
[1,2,4]triazin-5-il)fenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-{1-[(dimetilamino)karbonil]piperidin-4-il}pirolo[2,1-f]
[1,2,4]triazin-5-il)fenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-{1-[(dimetilamino)karbonil]piperidin-4-il}pirolo[2,1-f]
[1,2,4]triazin-5-il)-3-fluorofenil]-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-{1-[(dimetilamino)karbonil]piperidin-4-il}pirolo[2,1-f]
[1,2,4]triazin-5-il)-3-fluorofenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-metoksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-metoksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-metoksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-metoksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}fenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo
[2,1-f][1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo
[2,1-f][1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo
[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-
5-il}fenil)-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid; i
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-
5-il}-3-fluorofenil)-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
ili njegova farmaceutski prihvatljiva sol; ili
(b) spoj se bira od sljedećih:
N-{4-[4-amino-7-(cis-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]
fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(trans-4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(4-hidroksicikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[7-(1-acetilpiperidin-4-il)-4-aminopirolo[2,1-f][1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-piperidin-4-ilpirolo[2,1-f][1,2,4]triazin-5-il)-3-fluorofenil]-
1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-[4-(4-amino-7-{1-[(dimetilamino)karbonil]piperidin-4-il}pirolo[2,1-f]
[1,2,4]triazin-5-il)-3-fluorofenil]-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-
3-karboksamid;
N-(4-{4-amino-7-[1-(2-metoksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-{4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-5-il}-3-fluorofenil)-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo[2,1-f]
[1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2-okso-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo[2,1-f]
[1,2,4]triazin-5-il]fenil}-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-{4-[4-amino-7-(1-{[etil(metil)amino]karbonil}piperidin-4-il)pirolo[2,1-f]
[1,2,4]triazin-5-il]-3-fluorofenil}-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-{4-[4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-
5-il}fenil)-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid; i
N-{4-[4-amino-7-[1-(2-hidroksietil)piperidin-4-il]pirolo[2,1-f][1,2,4]triazin-
5-il}3-fluorofenil)-1-(4-fluorofenil)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-
3-karboksamid;
ili njegova farmaceutski prihvatljiva sol; ili
(c) spoj se bira od sljedećih:
N-(4-(4-amino-7-(1-(dimetilkarbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(etil(metil)karbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-metilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-
1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(dimetilkarbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(4-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(etil(metil)karbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-3-(4-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(dimetilkarbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-etil-3-(4-fluorofenil)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(morfolin-4-karbonil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-etil-3-(4-fluorofenil)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(etil(metil)karbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-3-(2-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(dimetilkarbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-3-(3-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(3-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(dimetilkarbamoil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-etil-3-(3-fluorofenil)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-etil-3-(3-fluorofenil)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid; i
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-2,5-diokso-1-fenil-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
ili njegova farmaceutski prihvatljiva sol; ili
(d) spoj se bira od sljedećih:
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)-3-fluorofenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(2,5-difluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)-3-metilfenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(piridin-3-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid;
(R)-N-(4-(4-amino-7-(1-(2-hidroksipropanoil)piperidin-4-il)pirolo[1,2-f]
[1,2,4]triazin-5-il)fenil)-1-etil-3-(4-fluorofenil)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(ciklopropankarbonil)piperidin-4-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-(2-hidroksipropil)-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(2-(dimetilamino)-2-oksoetil)piperidin-4-il)pirolo
[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(1-metil-2-oksopirolidin-3-il)piperidin-4-il)pirolo
[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)
fenil)-1-izopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1,3,5-trimetil-1H-pirazol-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(3-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(6-(dimetilkarbamoil)-4-metilpiridin-3-il)pirolo[1,2-f]
[1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
4-amino-5-(4-(3-(3-fluorofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamido)fenil)-N,N-dimetilpirolo[2,1-f][1,2,4]
triazin-7-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-izopropil-3-(1-metil-1H-pirazol-4-il)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-izopropil-3-(1-metil-1H-pirazol-3-il)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-3-(2-metiltiazol-5-il)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-3-cikloheksil-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-3-(3-cijanofenil)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-izopropil-3-(5-metilizoksazol-3-il)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(4-(dimetilamino)cikloheksil)pirolo[2,1-f][1,2,4]triazin-5-il)
fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-(ciklopropankarbonil)azetidin-3-il)pirolo[1,2-f][1,2,4]
triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(morfolinometil)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-izopropil-6-metil-5-(1-metil-1H-pirazol-5-il)-4-okso-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5'-fluoro-1-izopropil-2-metil-4-okso-1,4-dihidro-[3,3'-bipiridin]-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-(3-cijanofenil)-1-izopropil-6-metil-4-okso-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-5-bromo-1-(5-fluoropiridin-3-il)-6-metil-2-okso-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-(cijanometil)-5'-fluoro-6-metil-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5'-fluoro-6-metil-2-okso-5-(tiazol-4-il)-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-okso-1-fenil-1,6-dihidro-[2,2'-bipiridin]-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6'-metil-6-okso-1-fenil-1,6-dihidro-[2,3'-bipiridin]-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-3-metil-6-okso-1-fenil-1,6-dihidro-[2,3'-bipiridin]-5-karboksamid;
N-{4-[4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-6-metil-5-(1-metil-1H-pirazol-4-il)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-6-metil-2-okso-1-fenil-5-pirimidin-2-il-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-metilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-6-metil-2-okso-1-fenil-5-pirimidin-2-il-1,2-dihidropiridin-3-karboksamid;
N-{4-[4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il]fenil}-6-metil-5-morfolin-4-il-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-cijano-6-metil-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N3-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)
fenil)-6-metil-2-okso-1-fenil-1,2-dihidropiridin-3,5-dikarboksamid;
5-acetil-N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-6-metil-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-(5-fluoropiridin-3-il)-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-7,7-dimetil-2,5-diokso-1-(piridin-3-il)-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-(5-fluoropiridin-3-il)-6,6-dimetil-2,5-diokso-1,2,5,6,7,8-heksahidrokinolin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-bromo-6-metil-2-okso-2H-[1,2'-bipiridin]-3-karboksamid; i
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-ciklopropil-6-metil-5-(oksazol-2-il)-4-okso-1,4-dihidropiridin-3-karboksamid;
ili njegova farmaceutski prihvatljiva sol; ili
(e) spoj se bira od sljedećih:
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5'-fluoro-5,6-dimetil-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-5-(cijanometil)-6-metil-2-okso-1-(piridin-2-il)-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(1-metil-1H-pirazol-5-il)-2-okso-2H-[1,2'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-kloro-6-metil-2-okso-2H-[1,2'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(1-metil-1H-pirazol-3-il)-2-okso-2H-[1,2'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(oksazol-2-il)-2-okso-2H-[1,2'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-(difluorometil)-6-metil-2-okso-2H-[1,2'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-4-okso-5-(piridin-3-il)-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-5-(5-fluoropiridin-3-il)-1-izopropil-4-okso-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-bromo-6-metil-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-kloro-6-metil-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5,6-dimetil-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(1-metil-1H-pirazol-4-il)-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(1-metil-1H-pirazol-5-il)-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-6-metil-5-(1-metil-1H-pirazol-3-il)-2-okso-2H-[1,3'-bipiridin]-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-bromo-6-(metoksimetil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-5-cijano-6-(etoksimetil)-2-okso-1-fenil-1,2-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-3-(1,4-dimetil-1H-pirazol-3-il)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)-1-ciklopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)- 1-ciklopropil-2,4-diokso-3-(piridin-3-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)- 1'-ciklopropil-2'-metil-4'-okso-1',4'-dihidro-[2,3'-bipiridin]-5'-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[2,1-f][1,2,4]triazin-5-il)fenil)- 1-ciklopropil-2,2'-dimetil-4-okso-1,4-dihidro-[3,3'-bipiridin]-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(pirimidin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-ciklopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-
karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(5-fluoropiridin-2-il)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-
karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-4-okso-5-(piridin-2-il)-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-ciklopropil-6-metil-4-okso-5-(piridin-3-il)-1,4-dihidropiridin-3-karboksamid;
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-3-(1,5-dimetil-1H-pirazol-3-il)-1-izopropil-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid; i
N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-3-(6-metilpiridin-2-il)-2,4-diokso-1,2,3,4-tetrahidropirimidin-5-karboksamid;
ili njegova farmaceutski prihvatljiva sol.
13. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid, ili njegova farmaceutski prihvatljiva sol.
14. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid.
15. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid, ili njegova farmaceutski prihvatljiva sol.
16. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid.
17. Farmaceutski pripravak, naznačen time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1-12, ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač.
18. Farmaceutski pripravak, naznačen time, da sadrži N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid, ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač.
19. Farmaceutski pripravak, naznačen time, da sadrži N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-(piridin-2-il)-1,2,3,4-tetrahidropirimidin-5-karboksamid, i farmaceutski prihvatljiv nosač.
20. Farmaceutski pripravak, naznačen time, da sadrži N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid, ili njegovu farmaceutski prihvatljivu sol, i farmaceutski prihvatljiv nosač.
21. Farmaceutski pripravak, naznačen time, da sadrži N-(4-(4-amino-7-(1-izobutirilpiperidin-4-il)pirolo[1,2-f][1,2,4]triazin-5-il)fenil)-1-izopropil-2,4-diokso-3-fenil-1,2,3,4-tetrahidropirimidin-5-karboksamid, i farmaceutski prihvatljiv nosač.
22. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 17-21, naznačen time, da je za uporabu u inhibiranju TAM kinaze.
23. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 17-21, naznačen time, da je za uporabu u inhibiranju AXL i MER kinaze.
24. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 17-21, naznačen time, da je za uporabu u liječenju raka kod pacijenta.
25. Spoj ili farmaceutski pripravak za uporabu prema patentnom zahtjevu 24, naznačen time, da:
(a) rak se bira od sljedećih: hepatocelularni rak, rak mokraćnog mjehura, rak dojke, rak cerviksa, kolorektalni rak, rak endometrija, rak želuca, rak glave i vrata, rak bubrega, rak jetre, rak pluća, rak jajnika, rak prostate, rak jednjaka, rak žučnog mjehura, rak gušterače, rak tiroidne žlijezde, rak kože, leukemija, multipli mijelom, kronični limfom limfocita, leukemija T stanica odraslih, limfom B stanica, akutna mijeloična leukemija, Hodgkinov ili ne-Hodgkinov limfom, Waldenstromova makroglobulinemija, limfom kosmatih stanica, Burkittov limfom, glioblastom, melanom, i rabdomiosarkom;
(b) rak je rak pluća, rak prostate, rak debelog crijeva, rak dojke, melanom, karcinom bubrežnih stanica, multipli mijelom, rak želuca, ili rabdomiosarkom; ili
(c) rak je rak glave i vrata.
26. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 17-21, naznačen time, da je za uporabu u liječenju sarkoma, pri čemu se sarkom bira od sljedećih: hondrosarkom, Ewingov sarkom, osteosarkom, rabdomiosarkom, angiosarkom, fibrosarkom, liposarkom, miksom, rabdomiom, rabdosarkom, fibrom, lipom, harmatom, i teratom.
27. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski pripravak prema bilo kojem od patentnih zahtjeva 17-21, naznačen time, da je za uporabu u medicini.
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PCT/US2017/024270 WO2017172596A1 (en) | 2016-03-28 | 2017-03-27 | Pyrrolotriazine compounds as tam inhibitors |
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Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017027717A1 (en) | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
KR20230111268A (ko) | 2016-03-28 | 2023-07-25 | 인사이트 코포레이션 | Tam 억제제로서 피롤로트리아진 화합물 |
JOP20190156B1 (ar) | 2016-12-23 | 2023-09-17 | Bayer Pharma AG | أميدات عطرية لحمض الكربوكسيليك بصفتها مضادات لمستقبلة البراديكينين b1 |
EP3673907A4 (en) | 2017-08-23 | 2020-08-19 | ONO Pharmaceutical Co., Ltd. | CANCER TREATMENT PHARMACEUTICAL INCLUDING AX1 INHIBITOR AS AN EFFECTIVE INGREDIENT |
EP3988552A1 (en) * | 2017-09-27 | 2022-04-27 | Incyte Corporation | Salts of pyrrolotriazine derivatives useful as tam inhibitors |
WO2019074116A1 (ja) | 2017-10-13 | 2019-04-18 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含む固形がん治療剤 |
US20210177828A1 (en) * | 2018-01-17 | 2021-06-17 | Nanjing Transthera Biosciences Co., Ltd. | Tam family kinase /and csf1r kinase inhibitor and use thereof |
EP3743430B1 (en) | 2018-01-26 | 2023-08-02 | Bristol-Myers Squibb Company | Aminopyrrolotriazines as kinase inhibitors |
CN110627796B (zh) * | 2018-06-21 | 2022-07-12 | 北京越之康泰生物医药科技有限公司 | 含氮杂环类衍生物及其在医药上的应用 |
AR117600A1 (es) * | 2018-06-29 | 2021-08-18 | Incyte Corp | Formulaciones de un inhibidor de axl / mer |
UY38349A (es) | 2018-08-30 | 2020-03-31 | Array Biopharma Inc | Compuestos de pirazolo[3,4-b]piridina como inhibidores de cinasas tam y met |
CN111689991B (zh) * | 2019-03-13 | 2023-06-09 | 习峰 | 取代的杂芳基化合物及其组合物和用途 |
CN110156836A (zh) * | 2019-06-10 | 2019-08-23 | 成家钢 | 一种环丙基羰基亚甲基三苯基磷的制备方法 |
EP4005637A4 (en) * | 2019-07-29 | 2023-07-19 | Takeda Pharmaceutical Company Limited | HETEROCYCLIC COMPOUND |
CN112409361B (zh) * | 2019-08-23 | 2022-08-16 | 山东轩竹医药科技有限公司 | Tam抑制剂及其用途 |
EP4029862A4 (en) * | 2019-09-06 | 2023-10-04 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences | CONNECTION WITH AXL AND C-MET KINASE INHIBITORY ACTIVITY, THEIR PREPARATION AND USE |
CN113336758B (zh) * | 2020-03-03 | 2022-08-19 | 北京桦冠医药科技有限公司 | 化合物7-碘吡咯并[2,1-f][1,2,4]三嗪-4-胺的一种新合成方法 |
IL296065A (en) | 2020-03-06 | 2022-10-01 | Incyte Corp | Combined treatment including axl/mer and pd-1/pd-l1 inhibitors |
CN111233870A (zh) * | 2020-03-11 | 2020-06-05 | 中国科学技术大学 | 用于快速制备瑞德西韦药物中间体的方法 |
WO2021233236A1 (zh) * | 2020-05-18 | 2021-11-25 | 北京范恩柯尔生物科技有限公司 | 取代的杂芳基化合物及其组合物和用途 |
CN113912628B (zh) * | 2020-07-10 | 2023-05-02 | 北京范恩柯尔生物科技有限公司 | 三嗪类化合物及其组合物和用途 |
WO2022166610A1 (zh) * | 2021-02-05 | 2022-08-11 | 四川科伦博泰生物医药股份有限公司 | 一类哒嗪酮杂环化合物及其制备方法和用途 |
WO2023016296A1 (zh) * | 2021-08-12 | 2023-02-16 | 四川科伦博泰生物医药股份有限公司 | 一类杂环化合物及其制备方法和用途 |
TW202330519A (zh) * | 2021-09-29 | 2023-08-01 | 香港商德琪研發有限公司 | 作為tam抑制劑的吡唑并吡啶化合物 |
WO2023155886A1 (en) * | 2022-02-17 | 2023-08-24 | Shanghai Antengene Corporation Limited | Pyrazolopyridine compounds as tam inhibitors |
WO2024054793A1 (en) | 2022-09-09 | 2024-03-14 | University Of Rochester | Inhibition of efferocytosis as a treatment to prevent bone loss and increase bone density and strength |
Family Cites Families (206)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5156840A (en) | 1982-03-09 | 1992-10-20 | Cytogen Corporation | Amine-containing porphyrin derivatives |
US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
US4908056A (en) | 1986-04-25 | 1990-03-13 | E. I. Du Pont De Nemours And Company | Heterocyclic acyl sulfonamides |
AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
EP0352575A3 (de) | 1988-07-28 | 1991-08-21 | Bayer Ag | Substituierte anellierte Pyrrole |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
LU91067I2 (fr) | 1991-06-14 | 2004-04-02 | Genentech Inc | Trastuzumab et ses variantes et dérivés immuno chimiques y compris les immotoxines |
ES2241710T3 (es) | 1991-11-25 | 2005-11-01 | Enzon, Inc. | Procedimiento para producir proteinas multivalentes de union a antigeno. |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
IT1269176B (it) | 1994-01-11 | 1997-03-21 | Isagro Srl | Eterobicicli ad attivita' fungicida |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
JP4436457B2 (ja) | 1995-08-18 | 2010-03-24 | モルフォシス アイピー ゲーエムベーハー | 蛋白質/(ポリ)ペプチドライブラリー |
JP2001520268A (ja) | 1997-10-14 | 2001-10-30 | ザ、プロクター、エンド、ギャンブル、カンパニー | 中鎖分枝鎖界面活性剤を包含する硬質表面クリーニング組成物 |
US6982265B1 (en) | 1999-05-21 | 2006-01-03 | Bristol Myers Squibb Company | Pyrrolotriazine inhibitors of kinases |
CN1390220A (zh) * | 1999-09-17 | 2003-01-08 | 艾博特股份有限两合公司 | 作为治疗剂的激酶抑制剂 |
US6770666B2 (en) | 1999-12-27 | 2004-08-03 | Japan Tobacco Inc. | Fused-ring compounds and use thereof as drugs |
CZ20013424A3 (cs) | 1999-12-27 | 2002-02-13 | Japan Tobacco Inc. | Sloučeniny s fúzovanými kruhy a jejich pouľití jako léčiva |
CA2413330A1 (en) | 2000-06-28 | 2002-01-03 | Smithkline Beecham P.L.C. | Wet milling process |
BR0208627A (pt) | 2001-04-06 | 2004-03-09 | Wyeth Corp | Combinações antineoplásicas tal como rapamicina junto com gencitabina ou fluorouracila |
AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
AU2003272175A1 (en) | 2002-10-21 | 2004-05-04 | Aprea Ab | Reactivation of wild type p53 in human tumour cells by a low molecular weight compound |
CA2506129C (en) | 2002-11-15 | 2015-02-17 | Idenix (Cayman) Limited | 2'-branched nucleosides and flaviviridae mutation |
EP2368578A1 (en) | 2003-01-09 | 2011-09-28 | Macrogenics, Inc. | Identification and engineering of antibodies with variant Fc regions and methods of using same |
CA2510003A1 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
US20050008625A1 (en) | 2003-02-13 | 2005-01-13 | Kalobios, Inc. | Antibody affinity engineering by serial epitope-guided complementarity replacement |
TW200505915A (en) | 2003-03-13 | 2005-02-16 | Synta Pharmaceuticals Corp | Fused pyrrole compounds |
JP2006520796A (ja) | 2003-03-17 | 2006-09-14 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼインヒビター |
WO2005003175A2 (en) | 2003-06-13 | 2005-01-13 | Biogen Idec Ma Inc. | Aglycosyl anti-cd154 (cd40 ligand) antibodies and uses thereof |
FR2857966A1 (fr) | 2003-07-24 | 2005-01-28 | Aventis Pharma Sa | Produits aryl-heteroaromatiques, compositions les contenant et utilisation |
CA2536408A1 (en) | 2003-08-22 | 2005-03-03 | Biogen Idec Ma Inc. | Improved antibodies having altered effector function and methods for making the same |
US20050203063A1 (en) | 2003-09-12 | 2005-09-15 | Raymond Deshaies | Proteasome pathway inhibitors and related methods |
US7306631B2 (en) | 2004-03-30 | 2007-12-11 | The Procter & Gamble Company | Keratin dyeing compounds, keratin dyeing compositions containing them, and use thereof |
UY28931A1 (es) | 2004-06-03 | 2005-12-30 | Bayer Pharmaceuticals Corp | Derivados de pirrolotriazina utiles para tratar trastornos hiper-proliferativos y enfermedades asociadas con angiogenesis |
AR053090A1 (es) * | 2004-07-20 | 2007-04-25 | Osi Pharm Inc | Imidazotriazinas como inhibidores de proteina quinasas y su uso para la preparacion de medicamentos |
US20070043057A1 (en) | 2005-02-09 | 2007-02-22 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
US20070015771A1 (en) | 2004-07-29 | 2007-01-18 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
UY29177A1 (es) | 2004-10-25 | 2006-05-31 | Astex Therapeutics Ltd | Derivados sustituidos de purina, purinona y deazapurina, composiciones que los contienen métodos para su preparación y sus usos |
CN101106983A (zh) | 2004-11-24 | 2008-01-16 | 诺瓦提斯公司 | JAK抑制剂与至少一种Bcr-Abl、Flt-3、FAK或RAF激酶抑制剂的组合 |
WO2006124874A2 (en) | 2005-05-12 | 2006-11-23 | Kalypsys, Inc. | Inhibitors of b-raf kinase |
WO2007056170A2 (en) | 2005-11-02 | 2007-05-18 | Bayer Healthcare Ag | Pyrrolo[2,1-f] [1,2,4] triazin-4-ylamines igf-1r kinase inhibitors for the treatment of cancer and other hyperproliferative diseases |
WO2007061737A2 (en) | 2005-11-17 | 2007-05-31 | Osi Pharmaceuticals, Inc. | FUSED BICYCLIC mTOR INHIBITORS |
US7514435B2 (en) | 2005-11-18 | 2009-04-07 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
JP5193876B2 (ja) | 2005-12-02 | 2013-05-08 | バイエル・ヘルスケア・エルエルシー | オーロラキナーゼの阻害により癌を処置するために有用なピロロトリアジン誘導体 |
PE20070855A1 (es) * | 2005-12-02 | 2007-10-14 | Bayer Pharmaceuticals Corp | Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas |
MX2008007103A (es) | 2005-12-02 | 2008-09-12 | Bayer Healthcare Llc | Derivados 4-amino-pirrolotriazina sustituidos, útiles para tratar trastornos hiperproliferativos y enfermedades asociadas con angiogenesis. |
EP2348023B9 (en) | 2005-12-13 | 2017-03-08 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
US7601713B2 (en) | 2005-12-15 | 2009-10-13 | Rigel Pharmaceuticals, Inc. | Kinase inhibitors and their uses |
JP5512975B2 (ja) | 2005-12-29 | 2014-06-04 | アッヴィ・インコーポレイテッド | タンパク質キナーゼ阻害薬 |
CA2649324A1 (en) | 2006-04-12 | 2007-10-25 | Jean-Damien Charrier | Tetrahydropteridines useful as inhibitors of protein kinases |
EA018917B1 (ru) | 2006-04-19 | 2013-11-29 | Новартис Аг | 6-о-замещенные бензоксазолы и бензотиазолы и способы подавления передачи сигналов от csf-1r |
EP2016077A2 (en) | 2006-04-25 | 2009-01-21 | Astex Therapeutics Limited | Pharmaceutical compounds |
EP2032560B1 (en) | 2006-06-29 | 2013-05-01 | Merck Sharp & Dohme Corp. | Substituted bicyclic and tricyclic thrombin receptor antagonists |
WO2008012635A2 (en) | 2006-07-26 | 2008-01-31 | Pfizer Products Inc. | Amine derivatives useful as anticancer agents |
WO2008045978A1 (en) | 2006-10-10 | 2008-04-17 | Rigel Pharmaceuticals, Inc. | Pinane-substituted pyrimidinediamine derivatives useful as axl inhibitors |
SI3034075T1 (sl) * | 2006-11-22 | 2018-12-31 | Incyte Holdings Corporation | Imidazotriazini in imidazopirimidini kot inhibitorji kinaze |
EP2428204A3 (en) | 2006-12-07 | 2012-07-04 | Schering Corporation | pH sensitive matrix formulation |
ES2359467T3 (es) | 2006-12-14 | 2011-05-23 | Vertex Pharmceuticals Incorporated | Compuestos útiles como inhibidores de proteína quinasas. |
PT2078010E (pt) | 2006-12-29 | 2014-05-07 | Rigel Pharmaceuticals Inc | Triazoles substituídos com heteroarilos policíclicos úteis como inibidores de axl |
US9650391B2 (en) | 2006-12-29 | 2017-05-16 | Rigel Pharmaceuticals Inc. | N3-heteroaryl substituted triazoles and N5-heteroaryl substituted triazoles useful as Axl inhibitors |
WO2008083353A1 (en) | 2006-12-29 | 2008-07-10 | Rigel Pharmaceuticals, Inc. | Bicyclic aryl and bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
EP2535345A1 (en) | 2007-01-12 | 2012-12-19 | BioCryst Pharmaceuticals, Inc. | Anticancer nucleoside analogs |
WO2008098139A2 (en) | 2007-02-07 | 2008-08-14 | The Regents Of The University Of Colorado | Axl tyrosine kinase inhibitors and methods of making and using the same |
US8124759B2 (en) | 2007-05-09 | 2012-02-28 | Abbott Laboratories | Inhibitors of protein kinases |
PL2155758T3 (pl) | 2007-05-10 | 2013-06-28 | Biocryst Pharm Inc | Pochodne tetrahydrofuro[3,4-d]dioksolanu przeznaczone do stosowania w leczeniu infekcji wirusowych i raka |
WO2009009016A1 (en) | 2007-07-06 | 2009-01-15 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
JP2010532756A (ja) | 2007-07-06 | 2010-10-14 | 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 | mTORC1及びmTORC2の両方の阻害剤を含む組み合わせ抗癌療法 |
US8461149B2 (en) | 2007-08-15 | 2013-06-11 | Vertex Pharmaceuticals Incorporated | Compounds useful as protein kinase inhibitors |
CN101820762B (zh) | 2007-09-25 | 2014-07-30 | 拜耳保健公司 | 透过抑制极光激酶而用于治疗癌症的吡咯并三嗪衍生物 |
GB0719803D0 (en) | 2007-10-10 | 2007-11-21 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
JP2011500778A (ja) | 2007-10-25 | 2011-01-06 | アストラゼネカ・アクチエボラーグ | ピリジン及びピラジン誘導体−083 |
SI2205592T1 (sl) | 2007-10-26 | 2013-09-30 | Rigel Pharmaceuticals, Inc. | Triazoli substituirani s policikličnim arilom in triazoli substituirani s policikličnim heteroarilom uporabni kot Axl inhibitorji |
DE102007051762A1 (de) | 2007-10-30 | 2009-05-07 | Bayer Healthcare Ag | Substituierte Pyrrolotriazine und ihre Verwendung |
WO2009085185A1 (en) | 2007-12-19 | 2009-07-09 | Amgen Inc. | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
AR070127A1 (es) | 2008-01-11 | 2010-03-17 | Novartis Ag | Pirrolo - pirimidinas y pirrolo -piridinas |
US8557814B2 (en) | 2008-03-19 | 2013-10-15 | OSI Pharmaceuticals, LLC | mTOR inhibitor salt forms |
US9206130B2 (en) | 2008-04-16 | 2015-12-08 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Quinoline derivatives as AXL kinase inhibitors |
AR071395A1 (es) | 2008-04-23 | 2010-06-16 | Gilead Sciences Inc | Analogos carba-nucleosidos 1'-sustituidos para tratamiento antiviral |
TWI539953B (zh) | 2008-04-28 | 2016-07-01 | 瑞波若斯治療學公司 | 用於治療乳癌之組成物和方法 |
KR20110039278A (ko) | 2008-06-23 | 2011-04-15 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제 억제제 |
KR20110018376A (ko) | 2008-06-23 | 2011-02-23 | 스미또모 가가꾸 가부시키가이샤 | 조성물 및 상기 조성물을 이용하여 이루어지는 발광 소자 |
WO2010002877A2 (en) | 2008-07-03 | 2010-01-07 | Biota Scientific Management | Bycyclic nucleosides and nucleotides as therapeutic agents |
JP5592884B2 (ja) | 2008-07-09 | 2014-09-17 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Axl阻害剤として有用な多環式ヘテロアリール置換トリアゾール |
EP2328888B1 (en) | 2008-07-09 | 2012-11-07 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
WO2010014755A1 (en) | 2008-07-29 | 2010-02-04 | The Regents Of The University Of Colorado | Methods and compounds for enhancing anti-cancer therapy |
US20100075973A1 (en) | 2008-08-28 | 2010-03-25 | Takeda Pharmaceutical Company Limited | Polo-like kinase inhibitors |
JP2012506238A (ja) | 2008-10-20 | 2012-03-15 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド,ア ボディー コーポレイト | インスリン様増殖因子−1受容体キナーゼ阻害剤に対する抗がん反応を予測する生物学的マーカー |
US8476282B2 (en) | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
EP2376491B1 (en) | 2008-12-19 | 2015-03-04 | Cephalon, Inc. | Pyrrolotriazines as alk and jak2 inhibitors |
EP2393814A1 (en) | 2009-02-09 | 2011-12-14 | SuperGen, Inc. | Pyrrolopyrimidinyl axl kinase inhibitors |
US20100204265A1 (en) | 2009-02-09 | 2010-08-12 | Genelabs Technologies, Inc. | Certain Nitrogen Containing Bicyclic Chemical Entities for Treating Viral Infections |
JP2012518657A (ja) | 2009-02-25 | 2012-08-16 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 併用抗癌治療 |
KR20100101054A (ko) | 2009-03-07 | 2010-09-16 | 주식회사 메디젠텍 | 세포핵에서 세포질로의 gsk3의 이동을 억제하는 화합물을 함유하는 세포핵에서 세포질로의 gsk3 이동에 의해 발생되는 질환의 치료 또는 예방용 약학적 조성물 |
US8765754B2 (en) | 2009-04-29 | 2014-07-01 | Locus Pharmaceuticals, Inc. | Pyrrolotriazine compounds |
CN102458581B (zh) | 2009-05-22 | 2016-03-30 | 因塞特控股公司 | 作为JANUS激酶抑制剂的吡唑-4-基-吡咯并[2,3-d]嘧啶和吡咯-3-基-吡咯并[2,3-d]嘧啶的N-(杂)芳基-吡咯烷衍生物 |
ME01838B (me) * | 2009-06-29 | 2014-12-20 | Lncyte Holdings Corp | Pirimidinoni kao inhibitori pi3k |
US20120128670A1 (en) | 2009-07-31 | 2012-05-24 | OSI Pharmaceuticals, LLC | mTOR INHIBITOR AND ANGIOGENESIS INHIBITOR COMBINATION THERAPY |
US9249145B2 (en) | 2009-09-01 | 2016-02-02 | Incyte Holdings Corporation | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
CR20190103A (es) | 2009-09-21 | 2019-09-19 | Gilead Sciences Inc | ANÁLOGOS DE CARBA-NUCLEÓSIDOS SUSTITUIDOS CON 2'-FLUORO PARA TRATAMIENTO ANTIVIRAL (Divisional 2012-0186) |
US8455451B2 (en) | 2009-09-21 | 2013-06-04 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
NZ599404A (en) | 2009-09-21 | 2014-02-28 | Gilead Sciences Inc | Processes and intermediates for the preparation of 1’-substituted carba-nucleoside analogs |
AU2010298190A1 (en) | 2009-09-25 | 2012-05-03 | Vertex Pharmaceuticals Incorporated | Methods for preparing pyrimidine derivatives useful as protein kinase inhibitors |
CN102665718B (zh) | 2009-10-06 | 2016-03-09 | 米伦纽姆医药公司 | 可用作pdk1抑制剂的杂环化合物 |
EP2311809A1 (en) | 2009-10-16 | 2011-04-20 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Quinolinyloxyphenylsulfonamides |
US8604217B2 (en) | 2009-11-12 | 2013-12-10 | Selvita S.A. | Compound, a process for its preparation, a pharmaceutical composition, use of a compound, a method for modulating or regulating serine/threonine kinases and a serine/threonine kinases modulating agent |
US8680108B2 (en) | 2009-12-18 | 2014-03-25 | Incyte Corporation | Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors |
CA2787714C (en) | 2010-01-22 | 2019-04-09 | Joaquin Pastor Fernandez | Inhibitors of pi3 kinase |
ME02386B (me) | 2010-03-10 | 2016-09-20 | Incyte Holdings Corp | Derivati piperidin-4-il azetidina kao inhibitori jak1 |
JP5752232B2 (ja) | 2010-03-31 | 2015-07-22 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | プロテインキナーゼ阻害剤としての置換ピロロトリアジン化合物 |
JP2013525481A (ja) | 2010-05-05 | 2013-06-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | PKC−θインヒビターとして有用な4置換ピラゾロピリミジン |
WO2011141713A1 (en) | 2010-05-13 | 2011-11-17 | Centro Nacional De Investigaciones Oncologicas (Cnio) | New bicyclic compounds as pi3-k and mtor inhibitors |
TW201201815A (en) | 2010-05-28 | 2012-01-16 | Gilead Sciences Inc | 1'-substituted-carba-nucleoside prodrugs for antiviral treatment |
GB2480814A (en) | 2010-06-01 | 2011-12-07 | Summit Corp Plc | Compounds for the treatment of clostridium difficile-associated disease |
JP5937073B2 (ja) | 2010-07-19 | 2016-06-22 | ギリード・サイエンシズ・インコーポレーテッド | ジアステレオマーとして純粋なホスホルアミデートプロドラッグの調製方法 |
PE20171155A1 (es) | 2010-07-22 | 2017-08-16 | Gilead Sciences Inc | Metodos y compuestos para tratar infecciones virales por paramyxoviridae |
EP2423208A1 (en) | 2010-08-28 | 2012-02-29 | Lead Discovery Center GmbH | Pharmaceutically active compounds as Axl inhibitors |
US20120077814A1 (en) | 2010-09-10 | 2012-03-29 | Zhong Wang | Sulfonamide, sulfamate, and sulfamothioate derivatives |
TW201305185A (zh) | 2010-09-13 | 2013-02-01 | Gilead Sciences Inc | 用於抗病毒治療之2’-氟取代之碳-核苷類似物 |
US9643969B2 (en) | 2010-09-29 | 2017-05-09 | Kissei Pharmaceutical Co., Ltd. | (aza)indolizine derivative and pharmaceutical use thereof |
AU2011313820A1 (en) | 2010-10-08 | 2013-04-11 | Biota Europe Ltd | Antibacterial compounds |
JP2013539759A (ja) | 2010-10-08 | 2013-10-28 | エラン ファーマシューティカルズ,インコーポレイテッド | ポロ様キナーゼの阻害剤 |
ITRM20100537A1 (it) | 2010-10-12 | 2012-04-12 | Consiglio Nazionale Ricerche | Aptamero inibitore del recettore tirosina chinasi axl per uso in terapia |
EP2640723A1 (en) | 2010-11-19 | 2013-09-25 | Incyte Corporation | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
US9034884B2 (en) | 2010-11-19 | 2015-05-19 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as JAK inhibitors |
EP2655374B1 (en) | 2010-12-20 | 2019-10-23 | Incyte Holdings Corporation | N-(1-(substituted-phenyl)ethyl)-9h-purin-6-amines as pi3k inhibitors |
AR085397A1 (es) | 2011-02-23 | 2013-09-25 | Intellikine Inc | Combinacion de inhibidores de quinasa y sus usos |
WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
MY181439A (en) | 2011-02-28 | 2020-12-22 | Sunshine Lake Pharma Co Ltd | Substituted quinoline compounds and methods of use |
MY161199A (en) | 2011-03-23 | 2017-04-14 | Amgen Inc | Fused tricyclic dual inhibitors of cdk 4/6 and flt3 |
EP2693881B1 (en) | 2011-04-01 | 2019-09-04 | University of Utah Research Foundation | Substituted n-phenylpyrimidin-2-amine analogs as inhibitors of the axl kinase |
ES2618489T3 (es) | 2011-05-04 | 2017-06-21 | Intellikine, Llc | Composiciones farmacéuticas combinadas y usos de las mismas |
WO2012154608A1 (en) | 2011-05-06 | 2012-11-15 | Intellikine, Llc | Reactive mtor and pi3 kinase inhibitors and uses thereof |
WO2012158795A1 (en) | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
WO2012158764A1 (en) | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
KR102052670B1 (ko) | 2011-05-17 | 2019-12-06 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 키나아제 저해제 |
AR086913A1 (es) | 2011-06-14 | 2014-01-29 | Novartis Ag | 4-metil-3-[[4-(3-piridinil)-2-pirimidinil]-amino]-n-[5-(4-metil-1h-imidazol-1-il)-3-(trifluoro-metil)-fenil]-benzamida amorfa, forma de dosificacion que la contiene y metodo para prepararlas |
US8691807B2 (en) | 2011-06-20 | 2014-04-08 | Incyte Corporation | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors |
KR20140036269A (ko) | 2011-07-01 | 2014-03-25 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | Alk1 억제제로서의 히드록시메틸아릴-치환된 피롤로트리아진 |
EP2548877A1 (en) | 2011-07-19 | 2013-01-23 | MSD Oss B.V. | 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors |
TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為jak抑制劑之環己基氮雜環丁烷衍生物 |
MX2020004502A (es) | 2011-09-02 | 2022-01-20 | Incyte Holdings Corp | Heterociclilaminas como inhibidores de fosfoinositida 3-cinasas (pi3k). |
US9376395B2 (en) | 2011-09-18 | 2016-06-28 | Purdue Pharmaceuticals Products L.P. | Pharmaceutical compositions |
CN102408411B (zh) | 2011-09-19 | 2014-10-22 | 北京康辰药业股份有限公司 | 一种含喹啉基的羟肟酸类化合物及其制备方法、以及含有该化合物的药物组合物及其应用 |
BR112014007788A2 (pt) | 2011-10-03 | 2017-04-18 | Univ North Carolina Chapel Hill | compostos de pirrolopirimidina para tratamento do câncer |
US20140377285A1 (en) | 2011-11-08 | 2014-12-25 | Intellikine, Llc | Treatment regimens using multiple pharmaceutical agents |
PL2780338T3 (pl) | 2011-11-14 | 2017-04-28 | Ignyta, Inc. | Pochodne uracylu jako inhibitory kinaz AXL i c-MET |
JP6130391B2 (ja) | 2011-11-23 | 2017-05-17 | インテリカイン, エルエルシー | Mtor阻害剤を使用する強化された治療レジメン |
WO2013085802A1 (en) | 2011-12-06 | 2013-06-13 | Merck Sharp & Dohme Corp. | Pyrrolopyrimidines as janus kinase inhibitors |
UY34484A (es) | 2011-12-15 | 2013-07-31 | Bayer Ip Gmbh | Benzotienilo-pirrolotriazinas disustituidas y sus usos |
EP2791143B1 (en) | 2011-12-15 | 2016-02-24 | Bayer Intellectual Property GmbH | Substituted benzothienyl-pyrrolotriazines and uses thereof in the treatment of cancer |
MX351812B (es) | 2012-01-31 | 2017-10-27 | Daiichi Sankyo Co Ltd | Derivados de piridona. |
WO2013113097A1 (en) | 2012-01-31 | 2013-08-08 | Beta Pharma Canada Inc. | Cyclic molecules as bruton's tyrosine kinase inhibitors |
US9475815B2 (en) | 2012-02-23 | 2016-10-25 | Bayer Intelletual Property Gmbh | Substituted benzothienyl-pyrrolotriazines and uses thereof |
US20150057243A1 (en) | 2012-04-02 | 2015-02-26 | Northern University | Compositions and Methods for the Inhibition of Methyltransferases |
CN103373996A (zh) | 2012-04-20 | 2013-10-30 | 山东亨利医药科技有限责任公司 | 作为crth2受体拮抗剂的二并环衍生物 |
WO2013162061A1 (ja) | 2012-04-26 | 2013-10-31 | 第一三共株式会社 | 二環性ピリミジン化合物 |
TW201406761A (zh) | 2012-05-18 | 2014-02-16 | Incyte Corp | 做爲jak抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物 |
DK2861599T3 (da) | 2012-06-18 | 2020-03-02 | Principia Biopharma Inc | Reversible kovalente pyrrolo- eller pyrazolopyrimidiner, der er nyttige til behandling af cancer og autoimmunsygdomme |
BR112014031798A2 (pt) | 2012-06-19 | 2017-06-27 | Sunovion Pharmaceuticals Inc | compostos de heteroaril e métodos de uso destes |
BR112014030147B1 (pt) | 2012-06-22 | 2019-10-15 | Sumitomo Chemical Company, Limited | Compostos heterocíclicos fundidos, composição e método para controlar pestes |
US9572811B2 (en) | 2012-08-03 | 2017-02-21 | Principia Biopharma Inc. | Treatment of dry eye |
WO2014035140A2 (en) | 2012-08-30 | 2014-03-06 | Kainos Medicine, Inc. | Compounds and compositions for modulating histone methyltransferase activity |
CA2883894C (en) | 2012-09-06 | 2020-08-18 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
WO2014042433A2 (en) | 2012-09-14 | 2014-03-20 | Kainos Medicine, Inc. | Compounds and compositions for modulating adenosine a3 receptor activity |
RU2015115631A (ru) * | 2012-09-26 | 2016-11-20 | Дзе Риджентс Оф Дзе Юниверсити Оф Калифорния | Модулирование ire1 |
WO2014062774A1 (en) | 2012-10-17 | 2014-04-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
EP2909210A4 (en) | 2012-10-17 | 2016-04-06 | Merck Sharp & Dohme | 2'-DISUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHOD FOR THE USE THEREOF FOR THE TREATMENT OF VIRUS DISEASES |
EP2909209B1 (en) | 2012-10-17 | 2022-08-03 | Merck Sharp & Dohme LLC | 2'-cyano substituted nucleoside derivatives and methods of use thereof for treatment of viral diseases |
PE20151141A1 (es) | 2012-11-01 | 2015-08-06 | Incyte Corp | Derivados triciclicos fusionados de tiofeno como inhibidores de jak |
EP2919785A4 (en) | 2012-11-16 | 2016-10-05 | Biocryst Pharm Inc | ANTIVIRAL NUCLEOSIDES CONTAINING AZASUCRE |
CN104936963B (zh) | 2012-11-20 | 2017-11-28 | 普罗齐纳斯有限公司 | 作为蛋白激酶抑制剂的硫醚衍生物 |
WO2014109858A1 (en) | 2013-01-14 | 2014-07-17 | Amgen Inc. | Methods of using cell-cycle inhibitors to modulate one or more properties of a cell culture |
JP6488239B2 (ja) | 2013-01-18 | 2019-03-20 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | Rock阻害剤としてのフタラジノンおよびイソキノリノン |
WO2014113942A1 (en) | 2013-01-23 | 2014-07-31 | Merck Sharp & Dohme Corp. | Btk inhibitors |
US20140357636A1 (en) | 2013-02-21 | 2014-12-04 | Wayne Rothbaum | Treatment of Skeletal-Related Disorders |
US9050345B2 (en) | 2013-03-11 | 2015-06-09 | Bristol-Myers Squibb Company | Pyrrolotriazines as potassium ion channel inhibitors |
US9012466B2 (en) | 2013-03-12 | 2015-04-21 | Arqule Inc. | Substituted tricyclic pyrazolo-pyrimidine compounds |
TWI649308B (zh) | 2013-07-24 | 2019-02-01 | 小野藥品工業股份有限公司 | 喹啉衍生物 |
EP3057970A1 (en) | 2013-10-18 | 2016-08-24 | Medivation Technologies, Inc. | Heterocyclic compounds and methods of use |
WO2015066371A1 (en) | 2013-10-31 | 2015-05-07 | Forum Pharmaceuticals, Inc. | SPIRO-OXADIAZOLINE COMPOUNDS AS AGONISTS OF α-7-NICOTINIC ACETYLCHOLINE RECEPTORS |
US9586967B2 (en) | 2013-11-08 | 2017-03-07 | Ono Pharmaceutical Co., Ltd. | Pyrrolo pyrimidine derivative |
MX2016009403A (es) * | 2014-02-03 | 2016-09-16 | Cadila Healthcare Ltd | Compuestos heterociclicos. |
CN106170488B (zh) | 2014-02-12 | 2020-09-18 | 弗门尼舍公司 | 用于取代的1-苄基-3-(1-(异噁唑-4-基甲基)-1h-吡唑-4-基)咪唑烷-2,4-二酮的合成的改进方法 |
ES2746839T3 (es) | 2014-12-18 | 2020-03-09 | Pfizer | Derivados de pirimidina y triazina y su uso como inhibidores de AXL |
WO2016183071A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Hetero-tricyclic compounds and their use for the treatment of cancer |
WO2017027717A1 (en) * | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
US10053465B2 (en) | 2015-08-26 | 2018-08-21 | Incyte Corporation | Pyrrolopyrimidine derivatives as TAM inhibitors |
WO2017062797A1 (en) | 2015-10-07 | 2017-04-13 | The University Of North Carolina At Chapel Hill | The methods for treatment of tumors |
CA3000803C (en) | 2015-10-13 | 2020-03-24 | Nihon Nohyaku Co., Ltd. | Oxime group-containing condensed heterocyclic compound or salt thereof, agricultural and horticultural insecticide comprising the compound, and method for using the insecticide |
US9920033B2 (en) | 2015-11-14 | 2018-03-20 | Calitor Sciences, Llc | Crystalline form of a substituted quinoline compound and pharmaceutical compositions thereof |
JP6905662B2 (ja) | 2015-11-14 | 2021-07-21 | サンシャイン・レイク・ファーマ・カンパニー・リミテッドSunshine Lake Pharma Co.,Ltd. | 置換キノリン化合物の結晶形およびその医薬組成物 |
KR20230111268A (ko) | 2016-03-28 | 2023-07-25 | 인사이트 코포레이션 | Tam 억제제로서 피롤로트리아진 화합물 |
PE20190377A1 (es) | 2016-04-22 | 2019-03-08 | Incyte Corp | Formulaciones de un inhibidor de lsd 1 |
AR108875A1 (es) | 2016-06-24 | 2018-10-03 | Incyte Corp | COMPUESTOS HETEROCÍCLICOS COMO INHIBIDORES DE PI3K-g |
JOP20170153A1 (ar) | 2016-07-15 | 2019-01-30 | Lilly Co Eli | نظائر urocortin-2 جديدة معدلة بحمض دهني لعلاج داء السكري وأمراض الكلى المزمنة |
PL3484524T3 (pl) | 2016-07-15 | 2023-03-20 | Ionis Pharmaceuticals, Inc. | Związki i sposoby modulacji smn2 |
EP3988552A1 (en) | 2017-09-27 | 2022-04-27 | Incyte Corporation | Salts of pyrrolotriazine derivatives useful as tam inhibitors |
AR117600A1 (es) | 2018-06-29 | 2021-08-18 | Incyte Corp | Formulaciones de un inhibidor de axl / mer |
IL296065A (en) | 2020-03-06 | 2022-10-01 | Incyte Corp | Combined treatment including axl/mer and pd-1/pd-l1 inhibitors |
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