CN1688575A - 抑制磷酸肌醇3-激酶β - Google Patents
抑制磷酸肌醇3-激酶β Download PDFInfo
- Publication number
- CN1688575A CN1688575A CN 03824362 CN03824362A CN1688575A CN 1688575 A CN1688575 A CN 1688575A CN 03824362 CN03824362 CN 03824362 CN 03824362 A CN03824362 A CN 03824362A CN 1688575 A CN1688575 A CN 1688575A
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- CN
- China
- Prior art keywords
- aryl
- methyl
- tgx
- pyrimidin
- pyrido
- Prior art date
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- 230000005764 inhibitory process Effects 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims abstract description 98
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims abstract description 98
- 238000000034 method Methods 0.000 claims abstract description 63
- 230000002785 anti-thrombosis Effects 0.000 claims abstract description 22
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims description 74
- CPRAGQJXBLMUEL-UHFFFAOYSA-N 9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1 CPRAGQJXBLMUEL-UHFFFAOYSA-N 0.000 claims description 61
- -1 [ (2-chlorophenyl) -methyl ] amino-7-methyl-2- (4-morpholinyl) -4H-pyrido [1, 2-a ] pyrimidin-4-one Chemical compound 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 229910052794 bromium Inorganic materials 0.000 claims description 30
- 239000003112 inhibitor Substances 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 229910052740 iodine Inorganic materials 0.000 claims description 27
- 239000003146 anticoagulant agent Substances 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
- BWCHMAXKQWYVNL-UHFFFAOYSA-N 8-(1-anilinoethyl)-6-methyl-2-pyridin-4-ylchromen-4-one Chemical compound C=1C(C)=CC(C(C=C(O2)C=3C=CN=CC=3)=O)=C2C=1C(C)NC1=CC=CC=C1 BWCHMAXKQWYVNL-UHFFFAOYSA-N 0.000 claims description 22
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- 150000001412 amines Chemical class 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 claims description 12
- 210000000265 leukocyte Anatomy 0.000 claims description 11
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 11
- 150000003254 radicals Chemical class 0.000 claims description 9
- ZYYBLCASOQNMSV-UHFFFAOYSA-N 7-methyl-9-[(n-methylanilino)methyl]-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1N(C)CC1=CC(C)=CN(C(C=2)=O)C1=NC=2N1CCOCC1 ZYYBLCASOQNMSV-UHFFFAOYSA-N 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 108091007960 PI3Ks Proteins 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- IRTDIKMSKMREGO-UHFFFAOYSA-N 2-[1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethylamino]benzoic acid Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1C(O)=O IRTDIKMSKMREGO-UHFFFAOYSA-N 0.000 claims description 6
- MQPPGUHRBJZXDR-UHFFFAOYSA-N 2-[1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethylamino]benzonitrile Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1C#N MQPPGUHRBJZXDR-UHFFFAOYSA-N 0.000 claims description 6
- MNYDDELZSLYLCK-UHFFFAOYSA-N 7-methyl-2-morpholin-4-yl-9-[1-[3-(trifluoromethyl)anilino]ethyl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC(C(F)(F)F)=C1 MNYDDELZSLYLCK-UHFFFAOYSA-N 0.000 claims description 6
- YOJDDYOKRDSTDE-UHFFFAOYSA-N 7-methyl-9-[1-(3-methylanilino)ethyl]-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC(C)=C1 YOJDDYOKRDSTDE-UHFFFAOYSA-N 0.000 claims description 6
- MQPSVIJKGXCEGQ-UHFFFAOYSA-N 9-[1-(3,4-dichloroanilino)ethyl]-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=C(Cl)C(Cl)=C1 MQPSVIJKGXCEGQ-UHFFFAOYSA-N 0.000 claims description 6
- XDLIVPXYLKDDJK-UHFFFAOYSA-N 9-[1-(3,5-difluoroanilino)ethyl]-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC(F)=CC(F)=C1 XDLIVPXYLKDDJK-UHFFFAOYSA-N 0.000 claims description 6
- QTZIMOLBWBGHEB-UHFFFAOYSA-N 9-[1-(3-chloroanilino)ethyl]-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC(Cl)=C1 QTZIMOLBWBGHEB-UHFFFAOYSA-N 0.000 claims description 6
- GJUODZZEMDJPKJ-UHFFFAOYSA-N 9-[1-(4-chloroanilino)ethyl]-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=C(Cl)C=C1 GJUODZZEMDJPKJ-UHFFFAOYSA-N 0.000 claims description 6
- 229940123225 PI3 kinase beta inhibitor Drugs 0.000 claims description 6
- 229940116355 PI3 kinase inhibitor Drugs 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 6
- KLHOSWGRCMNASW-UHFFFAOYSA-N 7-methyl-2-morpholin-4-yl-9-[1-(pyridin-2-ylamino)ethyl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=N1 KLHOSWGRCMNASW-UHFFFAOYSA-N 0.000 claims description 5
- VOKGKARHNCQWAZ-UHFFFAOYSA-N 7-methyl-2-morpholin-4-yl-9-[1-[2-(2h-tetrazol-5-yl)anilino]ethyl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1C=1N=NNN=1 VOKGKARHNCQWAZ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- FBZSEJLLDVYGSZ-UHFFFAOYSA-N 2-morpholin-4-yl-8-phenylmethoxychromen-4-one Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1OCC1=CC=CC=C1 FBZSEJLLDVYGSZ-UHFFFAOYSA-N 0.000 claims description 4
- IVKCFMPZKYEGBK-UHFFFAOYSA-N 2-morpholin-4-yl-9-(pyridin-3-ylmethoxy)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CN2C(=O)C=C(N3CCOCC3)N=C2C=1OCC1=CC=CN=C1 IVKCFMPZKYEGBK-UHFFFAOYSA-N 0.000 claims description 4
- PPJUDRAFEMEWSF-UHFFFAOYSA-N 3-amino-8-benzyl-2-morpholin-4-ylchromen-4-one Chemical compound N1(CCOCC1)C=1OC2=C(C(C=1N)=O)C=CC=C2CC1=CC=CC=C1 PPJUDRAFEMEWSF-UHFFFAOYSA-N 0.000 claims description 4
- ZYCUPVWTYRZSTN-UHFFFAOYSA-N 7-methyl-2-morpholin-4-yl-9-(pyridin-2-ylmethylamino)pyrido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(N3CCOCC3)=CC(=O)N2C=C(C)C=C1NCC1=CC=CC=N1 ZYCUPVWTYRZSTN-UHFFFAOYSA-N 0.000 claims description 4
- DKYOLXMEUOJGQB-UHFFFAOYSA-N 7-methyl-2-morpholin-4-yl-9-[1-(1,3-thiazol-2-ylamino)ethyl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=NC=CS1 DKYOLXMEUOJGQB-UHFFFAOYSA-N 0.000 claims description 4
- FRYHMUNWXOGGLA-MRXNPFEDSA-N 7-methyl-2-morpholin-4-yl-9-[[(1r)-1-phenylethyl]amino]pyrido[1,2-a]pyrimidin-4-one Chemical compound N([C@H](C)C=1C=CC=CC=1)C1=CC(C)=CN(C(C=2)=O)C1=NC=2N1CCOCC1 FRYHMUNWXOGGLA-MRXNPFEDSA-N 0.000 claims description 4
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- MHFWTFWRBOGPGH-UHFFFAOYSA-N 8-(3-methylphenyl)-2-morpholin-4-yl-1h-quinolin-4-one Chemical compound CC1=CC=CC(C=2C3=C(C(C=C(N3)N3CCOCC3)=O)C=CC=2)=C1 MHFWTFWRBOGPGH-UHFFFAOYSA-N 0.000 claims description 4
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- LLVIJSKMPLJKKS-UHFFFAOYSA-N 8-(4-fluorophenoxy)-2-morpholin-4-yl-1h-quinolin-4-one Chemical compound C1=CC(F)=CC=C1OC1=CC=CC2=C1NC(N1CCOCC1)=CC2=O LLVIJSKMPLJKKS-UHFFFAOYSA-N 0.000 claims description 4
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- XNDOAFNGHIXHPI-UHFFFAOYSA-N 8-benzyl-2-morpholin-4-ylchromen-4-one Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1CC1=CC=CC=C1 XNDOAFNGHIXHPI-UHFFFAOYSA-N 0.000 claims description 4
- ZUMQLEYNAIMZCC-UHFFFAOYSA-N 9-(anilinomethyl)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(N3CCOCC3)=CC(=O)N2C=C(C)C=C1CNC1=CC=CC=C1 ZUMQLEYNAIMZCC-UHFFFAOYSA-N 0.000 claims description 4
- UBJVUQITODDUCW-UHFFFAOYSA-N 9-(benzylamino)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(N3CCOCC3)=CC(=O)N2C=C(C)C=C1NCC1=CC=CC=C1 UBJVUQITODDUCW-UHFFFAOYSA-N 0.000 claims description 4
- OPDWSMWZLIHOJT-UHFFFAOYSA-N 9-[(2-methoxyphenyl)methylamino]-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CNC1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 OPDWSMWZLIHOJT-UHFFFAOYSA-N 0.000 claims description 4
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Abstract
Description
E.酶 | TGX-221IC50(μM) |
脂质激酶p110α-PI3Kp110β-PI3Kp110γ-PI3Kp110δ-PI3KPI4K酪氨酸激酶Ab1EGF受体FynHER2受体胰岛素受体Ser/Thr激酶酪蛋白激酶2Cdk2/细胞周期蛋白AERK1P38αP7086PKA非选择性PKC非选择性CaMK | 50.005>100.1>10>10>10>10>10>10>10>10>10>10>10>10>10>10 |
TGX# | 取代基形式 | α | β | γ | δ | 比率δ/β |
nM | ||||||
195 | 7-甲基-9-{[甲基(苯基)氨基]甲基} | >5000 | 20 | >5000 | 500 | 25.00 |
221 | 7-甲基-9-(1-苯基氨基乙基) | >5000 | 5 | >5000 | 100 | 20.00 |
239 | 9-[1-[(3,5-二氟苯基氨基)乙基]-7-甲基 | >5000 | 7 | >5000 | 80 | 11.43 |
243 | 9-[1-(4-氯苯基氨基)乙基]-7-甲基 | >5000 | 50 | >5000 | 2000 | 40.00 |
244 | 9-[1-(3,4-二氯苯基氨基)乙基]-7-甲基 | >5000 | 50 | >5000 | 1000 | 20.00 |
248 | 9-[1-(3-氯苯基氨基)乙基]-7-甲基 | >5000 | 10 | >5000 | 100 | 10.00 |
262 | 7-甲基-9-[1-(3-甲基苯基氨基)乙基] | >5000 | 50 | >5000 | 1000 | 20.00 |
264 | 7-甲基-9-[1-(3-三氟甲基苯基氨基)乙基] | >5000 | 75 | >5000 | 10000 | 133.33 |
295 | 7-甲基-9-[1-(2-吡啶基氨基)乙基] | >5000 | 50 | >5000 | 2000 | 40.00 |
分离的 酶测定(nM)IC50s | |||
方法 | 实施例8 | 实施例13 | |
# | 血小板IP(p85) | P110γ | P110δ |
TGX258 | 10000 | >20000 | >10000 |
TGX286 | 2 | 1000 | 100 |
KN303 | 10 | 1500 | 500 |
KN310 | 100 | 7500 | 1000 |
KN312 | 50 | 10000 | 10000 |
KN313 | 100 | 10000 | 5000 |
KN315 | >100 | 5000 | 5000 |
KN316 | 1000 | 20000 | 1000 |
KN317 | >100 | 20000 | 5000 |
KN319 | 500 | 20000 | 300 |
KN322 | 1000 | 10000 | 1000 |
KN326 | 500 | 5000 | 1000 |
分离的 酶测定(nM)IC50s | |||
方法 | 实施例8 | 实施例13 | |
# | 血小板IP(p85) | P110γ | P110δ |
KN327 | 20 | 15000 | 500 |
KN328 | 50 | 10000 | 10000 |
KN333 | 10000 | >10000 | |
KN335 | 1000 | 10000 | 1000 |
KN336 | 1000 | 10000 | 200 |
KN337 | 200 | >10000 | 200 |
KN340 | 10000 | >10000 | >10000 |
KN341 | 500 | 5000 | 50 |
KN342 | 10000 | >10000 | >10000 |
KN344 | 5000 | >10000 | |
KN345 | 5000 | >10000 | 10000 |
KN346 | >10000 | >10000 | 10000 |
KN347 | >10000 | >10000 | >10000 |
KN348 | >10000 | >10000 | >10000 |
KN349 | 500 | >10000 | 2000 |
KN350 | 500 | ||
KN351 | 500 |
P110α同种型 | P110β同种型 | 血小板聚集对CD9抗体 | 血栓形成抑制 | 从嗜中性白细胞中的ROS释放 | 抗增殖活性对U937细胞 | |
方法 | 实施例13 | 实施例13 | 实施例10 | 实施例12 | 实施例14 | 实施例16 |
# | IC50/(nM) | IC50/(nM) | IC50/(nM) | IC50/(nM) | IC50/(nM) | IC50/(nM) |
TGX-286 | 5000 | 2 | 100 | 500 | 5 | 5 |
KN-327 | 200 | 250 | 78 | 20 |
表IV | |||
毫克/片 | |||
片剂A | 片剂B | 片剂C | |
活性组分 | 25 | 25 | 25 |
微晶纤维素 | 13 | - | 7 |
乳糖 | 78 | 47 | - |
淀粉(玉米) | - | 9 | - |
淀粉(预凝胶化,NF15) | - | - | 32 |
羟乙酸淀粉钠 | 5 | - | - |
聚乙烯吡咯烷酮 | 3 | 3 | - |
硬脂酸镁 | 1 | 1 | 1 |
总共 | 125 | 85 | 85 |
片剂V | ||
毫克/片 | ||
片剂A | 片剂B | |
活性组分 | 25 | 25 |
微晶纤维素 | 10 | - |
乳糖 | - | 36 |
甘露醇 | 51 | 57 |
蔗糖 | - | 3 |
阿拉伯胶 | - | 3 |
聚乙烯吡咯烷酮 | 3 | - |
硬脂酸镁 | 1 | 1 |
总共 | 90 | 125 |
片剂VI | |
毫克/片 | |
活性组分 | 25 |
羟丙基甲基纤维素 | 25 |
(HPMC) | - |
聚卡波非 | 39 |
硬脂酸镁 | 1 |
总共 | 90 |
表VII | ||
毫克/胶囊 | ||
胶囊A | 胶囊B | |
活性组分 | 25 | - |
微晶纤维素 | 45 | - |
乳糖 | 153 | - |
淀粉(1500NF) | - | 117 |
羟乙酸淀粉钠 | - | 6 |
硬脂酸镁 | 2 | 2 |
总共 | 225 | 150 |
表VIII | ||
毫克/胶囊 | ||
胶囊A | 胶囊B | |
活性组分 | 25 | 25 |
Macrogol 4000 BP | 200 | - |
卵磷脂 | - | 100 |
花生油 | - | 100 |
总共 | 225 | 225 |
表IX | |
毫克/胶囊 | |
活性组分 | 25 |
微晶纤维素 | 123 |
乳糖 | 62 |
柠檬酸三乙酯 | 3 |
乙基纤维素 | 12 |
总共 | 225 |
表X | |
%重量 | |
活性组分 | 2 |
盐酸(柠檬酸盐缓冲液) | 适量至pH7 |
注射用水 | 至100% |
表XI | |
%重量 | |
活性组分 | 0.5 |
在柠檬酸盐缓冲液中的盐酸 | 适量至pH7 |
羟基苯甲酸甲酯 | 0.2 |
羟基苯甲酸丙酯 | 0.2 |
注射用水 | 至100% |
表XII | |
活性组分 | 0.05g |
苯甲醇 | 0.1g |
Glycofuro751 | 1.45g |
注射用水 | 适量至3.00ml |
表XIII | |
活性组分 | 0.05g |
山梨醇溶液 | 1.5g |
甘油 | 1.0g |
苯甲酸钠 | 0.005g |
矫味剂 | 0.0125ml |
表XIV | |
毫克/栓剂 | |
活性组分(63μm)1 | 50 |
硬脂肪,USP(Witepsol H15-dynamit Nobel) | 1950 |
总共 | 2000 |
表XV | |
%重量 | |
活性组分 | 0.25 |
乙醇 | 10 |
注射用水 | 19.75 |
Propellant22(氯二氟甲烷) | 70 |
总共 | 100 |
表XIV | |
毫克/子宫托 | |
活性组分(63μm)1 | 50 |
无水葡萄糖 | 470 |
马铃薯淀粉 | 473 |
硬脂酸镁 | 473 |
注射用水 | 1000 |
Claims (26)
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US60/403,639 | 2002-08-16 | ||
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Cited By (6)
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CN102781923A (zh) * | 2010-01-26 | 2012-11-14 | 贝林格尔.英格海姆国际有限公司 | 5-炔基-嘧啶化合物 |
CN103596948A (zh) * | 2011-04-13 | 2014-02-19 | 阿斯利康(瑞典)有限公司 | 用于治疗癌症的作为pi3-激酶抑制剂的苯并吡喃酮化合物 |
CN104470909A (zh) * | 2012-03-23 | 2015-03-25 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩的化合物 |
WO2023207881A1 (en) * | 2022-04-24 | 2023-11-02 | InventisBio Co., Ltd. | Compounds, preparation methods and uses thereof |
WO2024008122A1 (zh) * | 2022-07-07 | 2024-01-11 | 海创药业股份有限公司 | 一种pi3k抑制剂及其制备方法和用途 |
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US8193182B2 (en) * | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
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IL89840A (en) * | 1988-04-06 | 1996-10-31 | Lipha | Substituted flavonoid compounds and salts thereof their preparation and pharmaceutical composition containing them |
WO1990006921A1 (en) * | 1988-12-21 | 1990-06-28 | The Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
US5703075A (en) * | 1988-12-21 | 1997-12-30 | Pharmacia & Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
DK0525123T3 (da) * | 1990-06-20 | 1998-05-04 | Upjohn Co | Antiatherosklerotiske og antithrombotiske 1-benzopyran-4-oner og 2-amino-1,3-benzoxazin-4-oner |
NZ520300A (en) * | 2000-01-24 | 2004-05-28 | Kinacia Pty Ltd | Morpholino-substituted pyridopyrimidine, quinolone and benzopyranone derivatives that inhibit the enzyme phosphoinositide (PI) 3-kinase |
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2003
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Cited By (8)
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CN102781923A (zh) * | 2010-01-26 | 2012-11-14 | 贝林格尔.英格海姆国际有限公司 | 5-炔基-嘧啶化合物 |
CN102781923B (zh) * | 2010-01-26 | 2016-03-02 | 贝林格尔.英格海姆国际有限公司 | 5-炔基-嘧啶化合物 |
CN103596948A (zh) * | 2011-04-13 | 2014-02-19 | 阿斯利康(瑞典)有限公司 | 用于治疗癌症的作为pi3-激酶抑制剂的苯并吡喃酮化合物 |
CN103596948B (zh) * | 2011-04-13 | 2016-04-27 | 阿斯利康(瑞典)有限公司 | 用于治疗癌症的作为pi3-激酶抑制剂的苯并吡喃酮化合物 |
CN104470909A (zh) * | 2012-03-23 | 2015-03-25 | Ptc医疗公司 | 用于治疗脊髓性肌萎缩的化合物 |
WO2023207881A1 (en) * | 2022-04-24 | 2023-11-02 | InventisBio Co., Ltd. | Compounds, preparation methods and uses thereof |
WO2024008122A1 (zh) * | 2022-07-07 | 2024-01-11 | 海创药业股份有限公司 | 一种pi3k抑制剂及其制备方法和用途 |
WO2024051778A1 (en) * | 2022-09-09 | 2024-03-14 | InventisBio Co., Ltd. | Compounds, preparation methods and uses thereof |
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