MX2015006191A - Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana. - Google Patents
Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana.Info
- Publication number
- MX2015006191A MX2015006191A MX2015006191A MX2015006191A MX2015006191A MX 2015006191 A MX2015006191 A MX 2015006191A MX 2015006191 A MX2015006191 A MX 2015006191A MX 2015006191 A MX2015006191 A MX 2015006191A MX 2015006191 A MX2015006191 A MX 2015006191A
- Authority
- MX
- Mexico
- Prior art keywords
- methyl
- oxy
- ethyl
- pyrrolidin
- purine
- Prior art date
Links
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title claims description 13
- 239000003112 inhibitor Substances 0.000 title description 13
- 108091007960 PI3Ks Proteins 0.000 title description 6
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 259
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 208000006673 asthma Diseases 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 230000001404 mediated effect Effects 0.000 claims abstract description 15
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 201000011510 cancer Diseases 0.000 claims abstract description 8
- 102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 claims abstract description 7
- 101710204747 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 claims abstract description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract 3
- -1 chloro, methyl Chemical group 0.000 claims description 219
- 238000002360 preparation method Methods 0.000 claims description 99
- 125000000217 alkyl group Chemical group 0.000 claims description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 72
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 206010003246 arthritis Diseases 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 100
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 84
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 23
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims 13
- 125000004404 heteroalkyl group Chemical group 0.000 claims 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 9
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 8
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims 7
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical group 0.000 claims 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 4
- 150000002431 hydrogen Chemical group 0.000 claims 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 4
- 210000002345 respiratory system Anatomy 0.000 claims 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 3
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 2
- 206010014561 Emphysema Diseases 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- 208000003456 Juvenile Arthritis Diseases 0.000 claims 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- 208000011623 Obstructive Lung disease Diseases 0.000 claims 2
- 230000036428 airway hyperreactivity Effects 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 201000009961 allergic asthma Diseases 0.000 claims 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 2
- 206010006451 bronchitis Diseases 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 208000023819 chronic asthma Diseases 0.000 claims 2
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims 2
- 230000003111 delayed effect Effects 0.000 claims 2
- 208000024711 extrinsic asthma Diseases 0.000 claims 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 2
- 201000010659 intrinsic asthma Diseases 0.000 claims 2
- 230000000414 obstructive effect Effects 0.000 claims 2
- DGOYLVBDCVINQZ-UHFFFAOYSA-N oxane-4-carboxamide Chemical compound NC(=O)C1CCOCC1 DGOYLVBDCVINQZ-UHFFFAOYSA-N 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
- 230000000306 recurrent effect Effects 0.000 claims 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- MAGPRRMLAMDPPE-UHFFFAOYSA-N 1-[3-[8-(1h-indazol-5-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1OC1=NC=NC2=C1N=C(C=1C=C3C=NNC3=CC=1)N2C MAGPRRMLAMDPPE-UHFFFAOYSA-N 0.000 claims 1
- JGCKEPAGXKCVDS-UHFFFAOYSA-N 1-[3-[8-(1h-indazol-6-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1OC1=NC=NC2=C1N=C(C=1C=C3NN=CC3=CC=1)N2C JGCKEPAGXKCVDS-UHFFFAOYSA-N 0.000 claims 1
- XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-UHFFFAOYSA-N 0.000 claims 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- YEJJUJNTWYKFLS-UHFFFAOYSA-N 1-pyrrolidin-1-ylpropan-1-one Chemical compound CCC(=O)N1CCCC1 YEJJUJNTWYKFLS-UHFFFAOYSA-N 0.000 claims 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- ARAUEWKXKTYCHZ-UHFFFAOYSA-N 2-methyl-1,3-oxazole-4-carbaldehyde Chemical compound CC1=NC(C=O)=CO1 ARAUEWKXKTYCHZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- PQXVMEVPQIXYQE-UHFFFAOYSA-N 3-methoxyazetidine-1-carbaldehyde Chemical compound COC1CN(C=O)C1 PQXVMEVPQIXYQE-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- KLCCBXRSFBQLRF-UHFFFAOYSA-N 5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol-2-yl-[3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]methanone Chemical compound CCN1N=CC(C=2N(C3=NC=NC(OC4CN(CC4)C(=O)C4=NN5CCCC5=C4)=C3N=2)C)=C1C KLCCBXRSFBQLRF-UHFFFAOYSA-N 0.000 claims 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- ROWKBLNPTYYUKN-UHFFFAOYSA-N 8-(1-ethyl-5-methylpyrazol-4-yl)-9-methyl-6-(1-pyrimidin-4-ylpyrrolidin-3-yl)sulfanylpurine Chemical compound CCN1N=CC(C=2N(C3=NC=NC(SC4CN(CC4)C=4N=CN=CC=4)=C3N=2)C)=C1C ROWKBLNPTYYUKN-UHFFFAOYSA-N 0.000 claims 1
- OULGIZHLOPZVPS-UHFFFAOYSA-N C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N1)S(=O)(=O)C1CN(CC1)C(=O)C1CCOCC1)C Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N1)S(=O)(=O)C1CN(CC1)C(=O)C1CCOCC1)C OULGIZHLOPZVPS-UHFFFAOYSA-N 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- MGPMCLCIYYDECC-UHFFFAOYSA-N CCn1ncc(c1C)-c1nc2c(SC3CCN(C3)c3ncnc4sccc34)ncnc2n1C Chemical compound CCn1ncc(c1C)-c1nc2c(SC3CCN(C3)c3ncnc4sccc34)ncnc2n1C MGPMCLCIYYDECC-UHFFFAOYSA-N 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims 1
- NVSPJDGXKBDYIZ-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1=NC=CN2C=NN=C21 NVSPJDGXKBDYIZ-UHFFFAOYSA-N 0.000 claims 1
- QKWLNNAAIJWRDQ-UHFFFAOYSA-N [3-(7H-purin-2-yloxy)pyrrolidin-1-yl]-pyridin-2-ylmethanone Chemical compound N1=C(C=CC=C1)C(=O)N1CC(CC1)OC1=NC=C2N=CNC2=N1 QKWLNNAAIJWRDQ-UHFFFAOYSA-N 0.000 claims 1
- GHJUPLFJQXACRI-UHFFFAOYSA-N [3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]sulfanylpyrrolidin-1-yl]-(1-methylpyrazol-3-yl)methanone Chemical compound CCN1N=CC(C=2N(C3=NC=NC(SC4CN(CC4)C(=O)C4=NN(C)C=C4)=C3N=2)C)=C1C GHJUPLFJQXACRI-UHFFFAOYSA-N 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004419 alkynylene group Chemical group 0.000 claims 1
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims 1
- LOBLFGNATFREJF-UHFFFAOYSA-N cyclohexyl-[3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]methanone Chemical compound CCN1N=CC(C=2N(C3=NC=NC(OC4CN(CC4)C(=O)C4CCCCC4)=C3N=2)C)=C1C LOBLFGNATFREJF-UHFFFAOYSA-N 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Natural products O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
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- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
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- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 claims 1
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- 239000002253 acid Substances 0.000 description 29
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- 238000004587 chromatography analysis Methods 0.000 description 27
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- 239000003795 chemical substances by application Substances 0.000 description 21
- 229910000104 sodium hydride Inorganic materials 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
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- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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Applications Claiming Priority (2)
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| US201261727416P | 2012-11-16 | 2012-11-16 | |
| PCT/CN2013/001394 WO2014075392A1 (en) | 2012-11-16 | 2013-11-15 | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
Publications (1)
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| MX2015006191A true MX2015006191A (es) | 2015-08-10 |
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| MX2015006191A MX2015006191A (es) | 2012-11-16 | 2013-11-15 | Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana. |
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| US (1) | US9730940B2 (https=) |
| EP (1) | EP2920171B1 (https=) |
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| KR (1) | KR20150082613A (https=) |
| CN (1) | CN104918939B (https=) |
| AU (1) | AU2013347538B2 (https=) |
| BR (1) | BR112015011148A8 (https=) |
| CA (1) | CA2891009A1 (https=) |
| MX (1) | MX2015006191A (https=) |
| RU (1) | RU2658006C2 (https=) |
| WO (1) | WO2014075392A1 (https=) |
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| TWI621618B (zh) | 2013-03-13 | 2018-04-21 | 比利時商健生藥品公司 | 經取代２－氮雜雙環類及其作為食慾素受體調控劑之用途 |
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| CN109689663B (zh) * | 2016-09-14 | 2023-04-14 | 詹森药业有限公司 | Menin-mll相互作用的螺二环抑制剂 |
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| CN113620976B (zh) * | 2020-05-09 | 2023-09-26 | 中国医学科学院药物研究所 | 噻唑并嘧啶类化合物及其制备方法、用途和药物组合物 |
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| PT95516A (pt) * | 1989-10-06 | 1991-08-14 | Wellcome Found | Processo para a preparacao de derivados de 2',3'-didesoxi nucleosidos 6-substituidos |
| US5670501A (en) | 1994-09-01 | 1997-09-23 | Discovery Therapeutics, Inc. | N-substituted 9-alkyladenines |
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| SE0300456D0 (sv) * | 2003-02-19 | 2003-02-19 | Astrazeneca Ab | Novel compounds |
| BRPI0410654A (pt) * | 2003-06-12 | 2006-06-20 | Novo Nordisk As | composto, composição farmacêutica, uso de um composto, método para tratar um distúrbio de um paciente, e, processo para a preparação de um composto |
| CA2565037A1 (en) | 2004-04-28 | 2005-11-10 | Cv Therapeutics, Inc. | Purine derivatives as a1 adenosine receptor antagonists |
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| WO2011075643A1 (en) * | 2009-12-18 | 2011-06-23 | Incyte Corporation | Substituted heteroaryl fused derivatives as pi3k inhibitors |
| US20130079342A1 (en) * | 2010-06-30 | 2013-03-28 | Paul John Dransfield | Heterocyclic compounds and their uses |
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| EP2616442B8 (en) | 2010-09-14 | 2018-10-17 | Exelixis, Inc. | Inhibitors of pi3k-delta and methods of their use and manufacture |
| AR082986A1 (es) * | 2010-09-14 | 2013-01-23 | Exelixis Inc | DERIVADOS DE PURINA COMO INHIBIDORES DE PI3K-d, METODOS PARA SU PREPARACION, FORMULACIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN EL TRATAMIENTO DE ENFERMEDADES HIPERPROLIFERATIVAS |
| CN102838600A (zh) * | 2011-06-24 | 2012-12-26 | 山东亨利医药科技有限责任公司 | 苯基喹唑啉类PI3Kδ抑制剂 |
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- 2013-11-15 KR KR1020157015530A patent/KR20150082613A/ko not_active Withdrawn
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| JP2015537010A (ja) | 2015-12-24 |
| EP2920171A1 (en) | 2015-09-23 |
| AU2013347538B2 (en) | 2017-04-27 |
| US20150353552A1 (en) | 2015-12-10 |
| RU2658006C2 (ru) | 2018-06-19 |
| BR112015011148A8 (pt) | 2019-10-01 |
| RU2015122895A (ru) | 2017-01-10 |
| EP2920171A4 (en) | 2016-06-22 |
| CN104918939B (zh) | 2018-08-28 |
| EP2920171B1 (en) | 2018-08-29 |
| US9730940B2 (en) | 2017-08-15 |
| CA2891009A1 (en) | 2014-05-22 |
| CN104918939A (zh) | 2015-09-16 |
| KR20150082613A (ko) | 2015-07-15 |
| AU2013347538A1 (en) | 2015-05-07 |
| BR112015011148A2 (pt) | 2017-07-11 |
| WO2014075392A1 (en) | 2014-05-22 |
| JP6297582B2 (ja) | 2018-03-20 |
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