JP2013518904A5 - - Google Patents
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- Publication number
- JP2013518904A5 JP2013518904A5 JP2012552123A JP2012552123A JP2013518904A5 JP 2013518904 A5 JP2013518904 A5 JP 2013518904A5 JP 2012552123 A JP2012552123 A JP 2012552123A JP 2012552123 A JP2012552123 A JP 2012552123A JP 2013518904 A5 JP2013518904 A5 JP 2013518904A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- halo
- substituted
- alkoxy
- cyano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 108091000080 Phosphotransferase Proteins 0.000 claims description 4
- 102000020233 phosphotransferase Human genes 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims 61
- 125000005843 halogen group Chemical group 0.000 claims 50
- 125000003545 alkoxy group Chemical group 0.000 claims 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims 25
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 15
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 13
- 239000008194 pharmaceutical composition Substances 0.000 claims 13
- 125000003118 aryl group Chemical group 0.000 claims 12
- -1 3,3,3-trifluoropropyl Chemical group 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 6
- 201000011510 cancer Diseases 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 6
- 229940124597 therapeutic agent Drugs 0.000 claims 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 5
- DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 claims 5
- 125000001153 fluoro group Chemical group F* 0.000 claims 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 3
- 239000000654 additive Substances 0.000 claims 3
- 125000005842 heteroatom Chemical group 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- 208000003200 Adenoma Diseases 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims 2
- 201000009030 Carcinoma Diseases 0.000 claims 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 229930195725 Mannitol Natural products 0.000 claims 2
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims 2
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 229920002472 Starch Polymers 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 2
- 230000000996 additive effect Effects 0.000 claims 2
- 239000000730 antalgic agent Substances 0.000 claims 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 2
- 239000000935 antidepressant agent Substances 0.000 claims 2
- 229940005513 antidepressants Drugs 0.000 claims 2
- 229940125683 antiemetic agent Drugs 0.000 claims 2
- 239000002111 antiemetic agent Substances 0.000 claims 2
- 210000000013 bile duct Anatomy 0.000 claims 2
- 208000015322 bone marrow disease Diseases 0.000 claims 2
- 239000001913 cellulose Substances 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 claims 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 2
- 210000001508 eye Anatomy 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 239000000594 mannitol Substances 0.000 claims 2
- 235000010355 mannitol Nutrition 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- AHOYCZFUOQKTMG-UHFFFAOYSA-N n-[4-[7-(ethylamino)-1-methyl-2-oxo-1,6-naphthyridin-3-yl]-3,5-difluoropyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(C=2C(N(C)C3=CC(NCC)=NC=C3C=2)=O)=C1F AHOYCZFUOQKTMG-UHFFFAOYSA-N 0.000 claims 2
- 210000000653 nervous system Anatomy 0.000 claims 2
- 239000003921 oil Substances 0.000 claims 2
- 235000019198 oils Nutrition 0.000 claims 2
- 230000002611 ovarian Effects 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
- 102000009929 raf Kinases Human genes 0.000 claims 2
- 108010077182 raf Kinases Proteins 0.000 claims 2
- 239000000600 sorbitol Substances 0.000 claims 2
- 235000010356 sorbitol Nutrition 0.000 claims 2
- 235000019698 starch Nutrition 0.000 claims 2
- 239000008107 starch Substances 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims 1
- 229920001817 Agar Polymers 0.000 claims 1
- 239000005995 Aluminium silicate Substances 0.000 claims 1
- 101100181041 Arabidopsis thaliana KINUA gene Proteins 0.000 claims 1
- 241000416162 Astragalus gummifer Species 0.000 claims 1
- 229920002261 Corn starch Polymers 0.000 claims 1
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 claims 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims 1
- 239000001856 Ethyl cellulose Substances 0.000 claims 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 claims 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 claims 1
- 108010010803 Gelatin Proteins 0.000 claims 1
- 229920002907 Guar gum Polymers 0.000 claims 1
- 101710113864 Heat shock protein 90 Proteins 0.000 claims 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims 1
- 244000020551 Helianthus annuus Species 0.000 claims 1
- 235000003222 Helianthus annuus Nutrition 0.000 claims 1
- 244000043261 Hevea brasiliensis Species 0.000 claims 1
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 claims 1
- 108091054455 MAP kinase family Proteins 0.000 claims 1
- 102000043136 MAP kinase family Human genes 0.000 claims 1
- 240000003183 Manihot esculenta Species 0.000 claims 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 claims 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 1
- 229920000881 Modified starch Polymers 0.000 claims 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 1
- 108091007960 PI3Ks Proteins 0.000 claims 1
- 102000038030 PI3Ks Human genes 0.000 claims 1
- 235000019483 Peanut oil Nutrition 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 108091008611 Protein Kinase B Proteins 0.000 claims 1
- 108090000315 Protein Kinase C Proteins 0.000 claims 1
- 102000003923 Protein Kinase C Human genes 0.000 claims 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 claims 1
- 229940123690 Raf kinase inhibitor Drugs 0.000 claims 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims 1
- 235000021355 Stearic acid Nutrition 0.000 claims 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 1
- 229920001615 Tragacanth Polymers 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000008272 agar Substances 0.000 claims 1
- 235000010419 agar Nutrition 0.000 claims 1
- 235000010443 alginic acid Nutrition 0.000 claims 1
- 239000000783 alginic acid Substances 0.000 claims 1
- 229920000615 alginic acid Polymers 0.000 claims 1
- 229960001126 alginic acid Drugs 0.000 claims 1
- 150000004781 alginic acids Chemical class 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- 235000010210 aluminium Nutrition 0.000 claims 1
- 235000012211 aluminium silicate Nutrition 0.000 claims 1
- 229940035676 analgesics Drugs 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 230000001430 anti-depressive effect Effects 0.000 claims 1
- 230000003474 anti-emetic effect Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 229910000019 calcium carbonate Inorganic materials 0.000 claims 1
- 235000010216 calcium carbonate Nutrition 0.000 claims 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims 1
- 235000013539 calcium stearate Nutrition 0.000 claims 1
- 239000008116 calcium stearate Substances 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims 1
- 235000010980 cellulose Nutrition 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 229920002301 cellulose acetate Polymers 0.000 claims 1
- 235000005687 corn oil Nutrition 0.000 claims 1
- 239000002285 corn oil Substances 0.000 claims 1
- 239000008120 corn starch Substances 0.000 claims 1
- 235000012343 cottonseed oil Nutrition 0.000 claims 1
- 239000002385 cottonseed oil Substances 0.000 claims 1
- 229960000913 crospovidone Drugs 0.000 claims 1
- 229940096516 dextrates Drugs 0.000 claims 1
- 235000019325 ethyl cellulose Nutrition 0.000 claims 1
- 229920001249 ethyl cellulose Polymers 0.000 claims 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims 1
- 229940093471 ethyl oleate Drugs 0.000 claims 1
- 239000004744 fabric Substances 0.000 claims 1
- 229920000159 gelatin Polymers 0.000 claims 1
- 239000008273 gelatin Substances 0.000 claims 1
- 235000019322 gelatine Nutrition 0.000 claims 1
- 235000011852 gelatine desserts Nutrition 0.000 claims 1
- 235000011187 glycerol Nutrition 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 claims 1
- 239000000665 guar gum Substances 0.000 claims 1
- 235000010417 guar gum Nutrition 0.000 claims 1
- 229960002154 guar gum Drugs 0.000 claims 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims 1
- 229940059904 light mineral oil Drugs 0.000 claims 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 claims 1
- 239000000391 magnesium silicate Substances 0.000 claims 1
- 235000019792 magnesium silicate Nutrition 0.000 claims 1
- 229910052919 magnesium silicate Inorganic materials 0.000 claims 1
- 235000019359 magnesium stearate Nutrition 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims 1
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims 1
- 229920000609 methyl cellulose Polymers 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 239000001923 methylcellulose Substances 0.000 claims 1
- 235000010981 methylcellulose Nutrition 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 1
- 239000008108 microcrystalline cellulose Substances 0.000 claims 1
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 1
- FVHBOSHZDUYWNH-UHFFFAOYSA-N n-[3,5-difluoro-4-[8-methyl-2-(methylamino)-7-oxopyrido[2,3-d]pyrimidin-6-yl]pyridin-2-yl]-3,3,3-trifluoropropane-1-sulfonamide Chemical compound O=C1N(C)C2=NC(NC)=NC=C2C=C1C1=C(F)C=NC(NS(=O)(=O)CCC(F)(F)F)=C1F FVHBOSHZDUYWNH-UHFFFAOYSA-N 0.000 claims 1
- NCHXQXSXDSAZBM-UHFFFAOYSA-N n-[3,5-difluoro-4-[8-methyl-2-(methylamino)-7-oxopyrido[2,3-d]pyrimidin-6-yl]pyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(C=2C(N(C)C3=NC(NC)=NC=C3C=2)=O)=C1F NCHXQXSXDSAZBM-UHFFFAOYSA-N 0.000 claims 1
- GUSVUXWCBQSCEW-UHFFFAOYSA-N n-[3,5-difluoro-4-[[3-[6-(2-methylsulfonylethylamino)pyrimidin-4-yl]pyrazin-2-yl]amino]pyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(NCCS(C)(=O)=O)C=2)=C1F GUSVUXWCBQSCEW-UHFFFAOYSA-N 0.000 claims 1
- FRZDSBAWMXEVKI-UHFFFAOYSA-N n-[3,5-difluoro-4-[[3-[6-(3,3,3-trifluoropropylamino)pyrimidin-4-yl]pyrazin-2-yl]amino]pyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(NCCC(F)(F)F)C=2)=C1F FRZDSBAWMXEVKI-UHFFFAOYSA-N 0.000 claims 1
- SPEYIAAXFDEAPI-UHFFFAOYSA-N n-[4-[7-(2-cyanoethylamino)-1-methyl-2-oxo-1,6-naphthyridin-3-yl]-3,5-difluoropyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(C=2C(N(C)C3=CC(NCCC#N)=NC=C3C=2)=O)=C1F SPEYIAAXFDEAPI-UHFFFAOYSA-N 0.000 claims 1
- UAMQGSIFFQINIK-UHFFFAOYSA-N n-[4-[[3-[6-(2,2-difluoroethylamino)pyrimidin-4-yl]pyrazin-2-yl]amino]-3,5-difluoropyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(NCC(F)F)C=2)=C1F UAMQGSIFFQINIK-UHFFFAOYSA-N 0.000 claims 1
- IDYSUCPTQVMXIW-UHFFFAOYSA-N n-[4-[[3-[6-(2-cyanoethylamino)pyrimidin-4-yl]pyrazin-2-yl]amino]-3,5-difluoropyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(NCCC#N)C=2)=C1F IDYSUCPTQVMXIW-UHFFFAOYSA-N 0.000 claims 1
- ATILRMFQWBMMEN-UHFFFAOYSA-N n-[4-[[3-[6-(ethylamino)pyrimidin-4-yl]pyrazin-2-yl]amino]-3,5-difluoropyridin-2-yl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=NC=C(F)C(NC=2C(=NC=CN=2)C=2N=CN=C(NCC)C=2)=C1F ATILRMFQWBMMEN-UHFFFAOYSA-N 0.000 claims 1
- 229920003052 natural elastomer Polymers 0.000 claims 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims 1
- 239000004006 olive oil Substances 0.000 claims 1
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- 102000051624 phosphatidylethanolamine binding protein Human genes 0.000 claims 1
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- 229960000540 polacrilin potassium Drugs 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 claims 1
- 229920001592 potato starch Polymers 0.000 claims 1
- 229920003124 powdered cellulose Polymers 0.000 claims 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000008159 sesame oil Substances 0.000 claims 1
- 235000011803 sesame oil Nutrition 0.000 claims 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims 1
- 239000000377 silicon dioxide Substances 0.000 claims 1
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- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 claims 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 1
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| WO2011097526A1 (en) * | 2010-02-05 | 2011-08-11 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
| CN105283454B (zh) * | 2013-04-12 | 2019-10-29 | 阿萨纳生物科技有限责任公司 | 作为ras/raf/mek/erk和pi3k/akt/pten/mtor通路双重抑制剂的喹唑啉和氮杂喹唑啉 |
| WO2014179498A1 (en) * | 2013-04-30 | 2014-11-06 | Genentech, Inc. | Serine/threonine kinase inhibitors |
| WO2014206344A1 (en) | 2013-06-28 | 2014-12-31 | Beigene, Ltd. | Fused tricyclic amide compounds as multiple kinase inhibitors |
| EP3579872A1 (en) | 2017-02-10 | 2019-12-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancers associated with activation of the mapk pathway |
| CA3086765A1 (en) | 2017-12-28 | 2019-07-04 | Tract Pharmaceuticals, Inc. | Stem cell culture systems for columnar epithelial stem cells, and uses related thereto |
| TWI831829B (zh) | 2018-09-12 | 2024-02-11 | 美商建南德克公司 | 苯氧基-吡啶基-嘧啶化合物及使用方法 |
| CN109078189A (zh) * | 2018-10-23 | 2018-12-25 | 黄泳华 | 含有蛋白激酶抑制剂与白藜芦醇的组合物 |
| CN109157660A (zh) * | 2018-10-28 | 2019-01-08 | 黄泳华 | 含有蛋白激酶抑制剂与西地那非的组合物 |
| WO2020142612A1 (en) * | 2019-01-03 | 2020-07-09 | Genentech, Inc. | Pyrido-pyrimidinone and pteridinone compounds as inhibitors of endoribonuclease inositol requiring enzyme i (ire i alpha) for the treatment of cancer diseases. |
| IL310931A (en) * | 2021-09-10 | 2024-04-01 | Black Diamond Therapeutics Inc | 6-aza-quinoline derivatives and related uses |
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| US6358932B1 (en) | 1994-05-31 | 2002-03-19 | Isis Pharmaceticals, Inc. | Antisense oligonucleotide inhibition of raf gene expression |
| US6391636B1 (en) | 1994-05-31 | 2002-05-21 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of raf gene expression |
| US6037136A (en) | 1994-10-24 | 2000-03-14 | Cold Spring Harbor Laboratory | Interactions between RaF proto-oncogenes and CDC25 phosphatases, and uses related thereto |
| US5717100A (en) | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
| IL127210A0 (en) | 1996-05-23 | 1999-09-22 | Applied Research Systems | Compounds inhibiting the binding of raf-1 or 13-3-3 proteins to the beta-chain of il-2 pharmaceutical compositions containing them and their use |
| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US6187799B1 (en) | 1997-05-23 | 2001-02-13 | Onyx Pharmaceuticals | Inhibition of raf kinase activity using aryl ureas |
| GB9716557D0 (en) | 1997-08-06 | 1997-10-08 | Glaxo Group Ltd | Benzylidene-1,3-dihydro-indol-2-one derivatives having anti-cancer activity |
| US6022884A (en) | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
| US6204467B1 (en) | 1998-03-24 | 2001-03-20 | Ford Global Technologies, Inc. | Method and apparatus for resistive welding |
| US7351834B1 (en) | 1999-01-13 | 2008-04-01 | Bayer Pharmaceuticals Corporation | ω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| HU230863B1 (hu) * | 1999-01-13 | 2018-10-29 | Bayer Healthcare Llc | Omega-karboxi-arilcsoporttal helyettesített difenil-karbamidok, mint raf-kináz inhibitorok |
| US6756410B2 (en) | 2000-08-30 | 2004-06-29 | Kamal D. Mehta | Induction of LDL receptor expression by extracellular-signal regulated kinase, ERK-1/2 |
| WO2005034869A2 (en) | 2003-10-08 | 2005-04-21 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| WO2007067444A1 (en) | 2005-12-08 | 2007-06-14 | Millennium Pharmaceuticals, Inc. | Bicyclic compounds with kinase inhibitory activity |
| EP2076513A1 (en) | 2006-10-20 | 2009-07-08 | Irm Llc | Compositions and methods for modulating c-kit and pdgfr receptors |
| WO2011097526A1 (en) * | 2010-02-05 | 2011-08-11 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
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- 2011-02-04 EP EP11703560.0A patent/EP2531498B1/en not_active Not-in-force
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