MX2015006192A - Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana. - Google Patents
Inhibidores de purina de fosfatidilinositol 3-quinasa delta humana.Info
- Publication number
- MX2015006192A MX2015006192A MX2015006192A MX2015006192A MX2015006192A MX 2015006192 A MX2015006192 A MX 2015006192A MX 2015006192 A MX2015006192 A MX 2015006192A MX 2015006192 A MX2015006192 A MX 2015006192A MX 2015006192 A MX2015006192 A MX 2015006192A
- Authority
- MX
- Mexico
- Prior art keywords
- purin
- ethyl
- amino
- pyrrolidin
- methyl
- Prior art date
Links
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 title description 15
- 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 319
- 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 16
- 230000001404 mediated effect Effects 0.000 claims abstract description 13
- 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
- 238000002360 preparation method Methods 0.000 claims description 203
- -1 chloro, methyl Chemical group 0.000 claims description 160
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 131
- 125000000217 alkyl group Chemical group 0.000 claims description 89
- 150000003839 salts Chemical class 0.000 claims description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 206010003246 arthritis Diseases 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 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
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 75
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 71
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 53
- 229960000643 adenine Drugs 0.000 claims 30
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 24
- 125000004404 heteroalkyl group Chemical group 0.000 claims 11
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 8
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims 6
- 125000000008 (C1-C10) alkyl group 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
- 208000003456 Juvenile Arthritis Diseases 0.000 claims 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 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
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 3
- 125000001188 haloalkyl group Chemical group 0.000 claims 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
- 206010014561 Emphysema Diseases 0.000 claims 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims 2
- 208000011623 Obstructive Lung disease Diseases 0.000 claims 2
- 208000020410 Psoriasis-related juvenile idiopathic arthritis 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
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims 2
- 230000003111 delayed effect Effects 0.000 claims 2
- 208000024711 extrinsic asthma Diseases 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
- 230000000414 obstructive effect Effects 0.000 claims 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 2
- 230000000306 recurrent effect Effects 0.000 claims 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- KYQNNKQWMYRULI-UHFFFAOYSA-N (2,5-dimethyl-1,3-oxazol-4-yl)-[3-[[9-ethyl-8-(2-methylpyrimidin-5-yl)purin-6-yl]amino]pyrrolidin-1-yl]methanone Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC(C1)CCN1C(=O)C=1N=C(C)OC=1C KYQNNKQWMYRULI-UHFFFAOYSA-N 0.000 claims 1
- UXMIWVISLJQNJQ-UHFFFAOYSA-N 1-[3-[(9-ethyl-8-methylpurin-6-yl)amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C)N2CC UXMIWVISLJQNJQ-UHFFFAOYSA-N 0.000 claims 1
- IFQPBOOTNHRBQE-UHFFFAOYSA-N 1-[3-[[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]amino]piperidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCCC1NC1=NC=NC2=C1N=C(C1=C(N(CC)N=C1)C)N2C IFQPBOOTNHRBQE-UHFFFAOYSA-N 0.000 claims 1
- XZTVMQMWAPLTFI-UHFFFAOYSA-N 1-[3-[[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C1=C(N(CC)N=C1)C)N2C XZTVMQMWAPLTFI-UHFFFAOYSA-N 0.000 claims 1
- RDMLKTNAOHEDTQ-UHFFFAOYSA-N 1-[3-[[8-(1h-indazol-5-yl)-9-methylpurin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C=1C=C3C=NNC3=CC=1)N2C RDMLKTNAOHEDTQ-UHFFFAOYSA-N 0.000 claims 1
- WNQPNFQACFFKON-UHFFFAOYSA-N 1-[3-[[8-(1h-indazol-6-yl)-9-methylpurin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C=1C=C3NN=CC3=CC=1)N2C WNQPNFQACFFKON-UHFFFAOYSA-N 0.000 claims 1
- OKHFDRAIGDVMND-UHFFFAOYSA-N 1-[3-[[8-(1h-indol-6-yl)-9-methylpurin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C=1C=C3NC=CC3=CC=1)N2C OKHFDRAIGDVMND-UHFFFAOYSA-N 0.000 claims 1
- MOHJKIVOFAEZSE-UHFFFAOYSA-N 1-[3-[[8-(difluoromethyl)-9-ethylpurin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C(F)F)N2CC MOHJKIVOFAEZSE-UHFFFAOYSA-N 0.000 claims 1
- QALKCKKNCJAETK-UHFFFAOYSA-N 1-[3-[[9-ethyl-8-(2-methylpropyl)purin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(CC(C)C)N2CC QALKCKKNCJAETK-UHFFFAOYSA-N 0.000 claims 1
- IDVDFMOYBQFSBB-UHFFFAOYSA-N 1-[3-[[9-ethyl-8-(2-methylpyrimidin-5-yl)purin-6-yl]amino]piperidin-1-yl]-2-methylpropan-1-one Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC1CCCN(C(=O)C(C)C)C1 IDVDFMOYBQFSBB-UHFFFAOYSA-N 0.000 claims 1
- NHQHLZBRLZVTTL-UHFFFAOYSA-N 1-[3-[[9-ethyl-8-(trifluoromethyl)purin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(C(F)(F)F)N2CC NHQHLZBRLZVTTL-UHFFFAOYSA-N 0.000 claims 1
- OXPQVRKTSGHGTB-UHFFFAOYSA-N 1-[3-[[9-methyl-8-(2-methylpropyl)purin-6-yl]amino]pyrrolidin-1-yl]propan-1-one Chemical compound C1N(C(=O)CC)CCC1NC1=NC=NC2=C1N=C(CC(C)C)N2C OXPQVRKTSGHGTB-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
- BBDYCTZQLPNUIB-UHFFFAOYSA-N 2-(fluoromethyl)cyclopropane-1-carbaldehyde Chemical compound FCC1C(C1)C=O BBDYCTZQLPNUIB-UHFFFAOYSA-N 0.000 claims 1
- ZXLBCMPKXNONCZ-UHFFFAOYSA-N 2-amino-1-[3-[[9-ethyl-8-(2-methylpyrimidin-5-yl)purin-6-yl]amino]pyrrolidin-1-yl]-2-methylpropan-1-one Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC1CCN(C(=O)C(C)(C)N)C1 ZXLBCMPKXNONCZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- SDPIXJJMLQIKSR-UHFFFAOYSA-N 3-[[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]amino]-1-(2-methylpropyl)pyrrolidin-2-one Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)NC1C(N(CC1)CC(C)C)=O)C SDPIXJJMLQIKSR-UHFFFAOYSA-N 0.000 claims 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
- PSAUDVOTVCGJOH-UHFFFAOYSA-N 6-[[1-(cyclobutanecarbonyl)pyrrolidin-3-yl]amino]-9-ethyl-n-(2,2,2-trifluoroethyl)purine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)NCC(F)(F)F)=NC2=C1NC(C1)CCN1C(=O)C1CCC1 PSAUDVOTVCGJOH-UHFFFAOYSA-N 0.000 claims 1
- VYVOCSWFODLOPE-UHFFFAOYSA-N 6-[[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]amino]-9-ethyl-n,n-dimethylpurine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)N(C)C)=NC2=C1NC(C1)CCN1C(=O)C1CC1 VYVOCSWFODLOPE-UHFFFAOYSA-N 0.000 claims 1
- PXQJLZGWLFDFHP-UHFFFAOYSA-N 6-[[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]amino]-9-ethyl-n-(2-methoxyethyl)purine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)NCCOC)=NC2=C1NC(C1)CCN1C(=O)C1CC1 PXQJLZGWLFDFHP-UHFFFAOYSA-N 0.000 claims 1
- SBIKYKNVXSNVEZ-UHFFFAOYSA-N 6-[[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]amino]-9-ethyl-n-(oxetan-3-yl)purine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)NC3COC3)=NC2=C1NC(C1)CCN1C(=O)C1CC1 SBIKYKNVXSNVEZ-UHFFFAOYSA-N 0.000 claims 1
- PRUGVLLZYGAAQX-UHFFFAOYSA-N 6-[[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]amino]-9-ethyl-n-phenylpurine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)NC=3C=CC=CC=3)=NC2=C1NC(C1)CCN1C(=O)C1CC1 PRUGVLLZYGAAQX-UHFFFAOYSA-N 0.000 claims 1
- DNRLNZVPSBUEBO-UHFFFAOYSA-N 6-[[1-(cyclopropanecarbonyl)pyrrolidin-3-yl]amino]-n-(cyclopropylmethyl)-9-ethylpurine-8-carboxamide Chemical compound N1=CN=C2N(CC)C(C(=O)NCC3CC3)=NC2=C1NC(C1)CCN1C(=O)C1CC1 DNRLNZVPSBUEBO-UHFFFAOYSA-N 0.000 claims 1
- REJPIVHCBUMHBJ-UHFFFAOYSA-N 9-ethyl-8-(2-methylpyrimidin-5-yl)-n-(1-pyridin-2-ylpyrrolidin-3-yl)purin-6-amine Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC(C1)CCN1C1=CC=CC=N1 REJPIVHCBUMHBJ-UHFFFAOYSA-N 0.000 claims 1
- SSXXHNAIFJNTNF-UHFFFAOYSA-N 9-ethyl-8-(2-methylpyrimidin-5-yl)-n-(1-pyrimidin-2-ylpyrrolidin-3-yl)purin-6-amine Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC(C1)CCN1C1=NC=CC=N1 SSXXHNAIFJNTNF-UHFFFAOYSA-N 0.000 claims 1
- QNBVTCGTDHHLCT-UHFFFAOYSA-N 9-ethyl-N-(1-isoquinolin-1-ylpyrrolidin-3-yl)-8-(2-methylpyrimidin-5-yl)purin-6-amine Chemical compound C(C)N1C2=NC=NC(=C2N=C1C=1C=NC(=NC1)C)NC1CN(CC1)C1=NC=CC2=CC=CC=C12 QNBVTCGTDHHLCT-UHFFFAOYSA-N 0.000 claims 1
- SBHGRGKVWJSLGS-UHFFFAOYSA-N 9-ethyl-n-[1-(6-methoxypyridin-2-yl)pyrrolidin-3-yl]-8-(2-methylpyrimidin-5-yl)purin-6-amine Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC(C1)CCN1C1=CC=CC(OC)=N1 SBHGRGKVWJSLGS-UHFFFAOYSA-N 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- DDDIIIUDDGNOPK-UHFFFAOYSA-N CC1=C(N=NS1)C(=O)N1CC(CC1)C1=NC(=C2N=CNC2=N1)N Chemical compound CC1=C(N=NS1)C(=O)N1CC(CC1)C1=NC(=C2N=CNC2=N1)N DDDIIIUDDGNOPK-UHFFFAOYSA-N 0.000 claims 1
- WHWFYGQVOSQYQA-UHFFFAOYSA-N CCn1c(nc2c(NC3CCN(C3)C(=O)N3CC(C3)OC)ncnc12)C(=O)NCC(F)(F)F Chemical compound CCn1c(nc2c(NC3CCN(C3)C(=O)N3CC(C3)OC)ncnc12)C(=O)NCC(F)(F)F WHWFYGQVOSQYQA-UHFFFAOYSA-N 0.000 claims 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- FJMNVSUWJVEXHR-UHFFFAOYSA-N [3-[(8-tert-butyl-9-ethylpurin-6-yl)amino]pyrrolidin-1-yl]-cyclopropylmethanone Chemical compound N1=CN=C2N(CC)C(C(C)(C)C)=NC2=C1NC(C1)CCN1C(=O)C1CC1 FJMNVSUWJVEXHR-UHFFFAOYSA-N 0.000 claims 1
- CDHAOCUUOAMMOI-UHFFFAOYSA-N [3-[[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]amino]azetidin-1-yl]-(oxan-4-yl)methanone Chemical compound CCN1N=CC(C=2N(C3=NC=NC(NC4CN(C4)C(=O)C4CCOCC4)=C3N=2)C)=C1C CDHAOCUUOAMMOI-UHFFFAOYSA-N 0.000 claims 1
- WFVKABQFHLSPFH-UHFFFAOYSA-N [3-[[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]amino]pyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound CCN1N=CC(C=2N(C3=NC=NC(NC4CN(CC4)C(=O)C4CCOCC4)=C3N=2)C)=C1C WFVKABQFHLSPFH-UHFFFAOYSA-N 0.000 claims 1
- OLJCGTWFJRUJHM-UHFFFAOYSA-N [3-[[8-(5-chloropyridin-3-yl)-9-ethylpurin-6-yl]amino]pyrrolidin-1-yl]-cyclopropylmethanone Chemical compound N1=CN=C2N(CC)C(C=3C=C(Cl)C=NC=3)=NC2=C1NC(C1)CCN1C(=O)C1CC1 OLJCGTWFJRUJHM-UHFFFAOYSA-N 0.000 claims 1
- WJTTZZDOGXZXRA-UHFFFAOYSA-N [3-[[8-(benzimidazol-1-yl)-9-ethylpurin-6-yl]amino]pyrrolidin-1-yl]-cyclopropylmethanone Chemical compound N1=CN=C2N(CC)C(N3C4=CC=CC=C4N=C3)=NC2=C1NC(C1)CCN1C(=O)C1CC1 WJTTZZDOGXZXRA-UHFFFAOYSA-N 0.000 claims 1
- OEADPOGZBWJIRS-UHFFFAOYSA-N [3-[[8-(difluoromethyl)-9-ethylpurin-6-yl]amino]pyrrolidin-1-yl]-(1,3-oxazol-4-yl)methanone Chemical compound CCn1c(nc2c(NC3CCN(C3)C(=O)c3cocn3)ncnc12)C(F)F OEADPOGZBWJIRS-UHFFFAOYSA-N 0.000 claims 1
- NDOXWSIBBHIJOY-PIJUOVFKSA-N [3-[[8-(difluoromethyl)-9-ethylpurin-6-yl]amino]pyrrolidin-1-yl]-[(2r)-1-methylpyrrolidin-2-yl]methanone Chemical compound N1=CN=C2N(CC)C(C(F)F)=NC2=C1NC(C1)CCN1C(=O)[C@H]1CCCN1C NDOXWSIBBHIJOY-PIJUOVFKSA-N 0.000 claims 1
- PIGUHLRPVFFTQD-UHFFFAOYSA-N [3-[[9-ethyl-8-(2-methylpyrimidin-5-yl)purin-6-yl]amino]pyrrolidin-1-yl]-(1,3-oxazol-4-yl)methanone Chemical compound N1=CN=C2N(CC)C(C=3C=NC(C)=NC=3)=NC2=C1NC(C1)CCN1C(=O)C1=COC=N1 PIGUHLRPVFFTQD-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- 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
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- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
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| WO2015188369A1 (en) * | 2014-06-13 | 2015-12-17 | Merck Sharp & Dohme Corp. | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
| KR101710127B1 (ko) * | 2014-08-29 | 2017-02-27 | 한화제약주식회사 | 야누스인산화효소 억제제로서의 치환된 N-(피롤리딘-3-일)-7H-피롤로[2,3-d]피리미딘-4-아민 |
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| CN108892635A (zh) * | 2018-09-07 | 2018-11-27 | 江苏工程职业技术学院 | 一种西沙必利关键中间体的制备方法 |
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| PT4069691T (pt) | 2019-12-06 | 2024-12-18 | Vertex Pharma | Tetrahidrofuranos substituídos como moduladores dos canais de sódio |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2112765C1 (ru) * | 1993-02-09 | 1998-06-10 | Дзе Велкам Фаундейшн Лимитед | ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ПРОЯВЛЯЮЩАЯ АКТИВНОСТЬ ПРОТИВ ВИРУСНОЙ ИНФЕКЦИИ И β D-АРАБИНОФУРАНОЗИЛ-2-АМИНО-6-МЕТОКСИ-9Н-ПУРИНЫ |
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| EP1165545A1 (en) * | 1999-03-26 | 2002-01-02 | AstraZeneca AB | Novel compounds |
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| JP4820290B2 (ja) | 2004-05-13 | 2011-11-24 | 第一三共株式会社 | 置換ピロリジン誘導体 |
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| UA112517C2 (uk) * | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| CA2812091C (en) * | 2010-09-14 | 2020-03-24 | Exelixis, Inc. | Inhibitors of pi3k-delta and methods of their use and manufacture |
| US9273028B2 (en) * | 2010-10-29 | 2016-03-01 | Biogen Ma Inc. | Heterocyclic tyrosine kinase inhibitors |
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| 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 |
-
2013
- 2013-11-15 KR KR1020157015531A patent/KR20150084992A/ko not_active Withdrawn
- 2013-11-15 WO PCT/CN2013/001395 patent/WO2014075393A1/en not_active Ceased
- 2013-11-15 MX MX2015006192A patent/MX2015006192A/es unknown
- 2013-11-15 CN CN201380070631.4A patent/CN104918940B/zh not_active Expired - Fee Related
- 2013-11-15 EP EP13855780.6A patent/EP2920172B1/en active Active
- 2013-11-15 AU AU2013347539A patent/AU2013347539B2/en not_active Ceased
- 2013-11-15 BR BR112015011147A patent/BR112015011147A8/pt not_active Application Discontinuation
- 2013-11-15 JP JP2015542135A patent/JP6322200B2/ja active Active
- 2013-11-15 RU RU2015122894A patent/RU2661896C2/ru not_active IP Right Cessation
- 2013-11-15 CA CA2891013A patent/CA2891013A1/en not_active Abandoned
- 2013-11-15 US US14/443,314 patent/US9938281B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US9938281B2 (en) | 2018-04-10 |
| JP2016502522A (ja) | 2016-01-28 |
| WO2014075393A1 (en) | 2014-05-22 |
| EP2920172A1 (en) | 2015-09-23 |
| RU2015122894A (ru) | 2017-01-10 |
| JP6322200B2 (ja) | 2018-05-09 |
| RU2661896C2 (ru) | 2018-07-23 |
| BR112015011147A2 (pt) | 2017-07-11 |
| EP2920172A4 (en) | 2016-05-25 |
| AU2013347539A1 (en) | 2015-05-07 |
| CA2891013A1 (en) | 2014-05-22 |
| CN104918940B (zh) | 2017-03-08 |
| BR112015011147A8 (pt) | 2019-10-01 |
| AU2013347539B2 (en) | 2017-06-15 |
| KR20150084992A (ko) | 2015-07-22 |
| EP2920172B1 (en) | 2019-12-25 |
| CN104918940A (zh) | 2015-09-16 |
| US20160207926A1 (en) | 2016-07-21 |
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