RU2595718C2 - Ингибиторы pi3-киназы и их применение - Google Patents
Ингибиторы pi3-киназы и их применение Download PDFInfo
- Publication number
- RU2595718C2 RU2595718C2 RU2012110024/04A RU2012110024A RU2595718C2 RU 2595718 C2 RU2595718 C2 RU 2595718C2 RU 2012110024/04 A RU2012110024/04 A RU 2012110024/04A RU 2012110024 A RU2012110024 A RU 2012110024A RU 2595718 C2 RU2595718 C2 RU 2595718C2
- Authority
- RU
- Russia
- Prior art keywords
- ring
- substituted
- nitrogen
- membered
- oxygen
- Prior art date
Links
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 title claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 155
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims abstract description 114
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims abstract description 39
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 229940116355 PI3 kinase inhibitor Drugs 0.000 claims abstract description 4
- 230000000694 effects Effects 0.000 claims abstract description 4
- 208000035475 disorder Diseases 0.000 claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 561
- 229910052757 nitrogen Inorganic materials 0.000 claims description 534
- 125000005842 heteroatom Chemical group 0.000 claims description 464
- 229910052760 oxygen Inorganic materials 0.000 claims description 458
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 455
- 239000001301 oxygen Chemical group 0.000 claims description 455
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 433
- 229910052717 sulfur Chemical group 0.000 claims description 420
- 229920006395 saturated elastomer Polymers 0.000 claims description 418
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 417
- 239000011593 sulfur Chemical group 0.000 claims description 417
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 147
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 138
- 125000002619 bicyclic group Chemical group 0.000 claims description 137
- 125000000623 heterocyclic group Chemical group 0.000 claims description 129
- 229910052736 halogen Inorganic materials 0.000 claims description 116
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 116
- 150000002367 halogens Chemical group 0.000 claims description 114
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 125000001931 aliphatic group Chemical group 0.000 claims description 104
- 108091007960 PI3Ks Proteins 0.000 claims description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims description 84
- 239000001257 hydrogen Substances 0.000 claims description 84
- 125000001072 heteroaryl group Chemical group 0.000 claims description 67
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 64
- 125000002837 carbocyclic group Chemical group 0.000 claims description 64
- 125000001424 substituent group Chemical group 0.000 claims description 50
- -1 sulfonyloxy Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 30
- 125000002950 monocyclic group Chemical group 0.000 claims description 28
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 26
- 101150065749 Churc1 gene Proteins 0.000 claims description 26
- 102100038239 Protein Churchill Human genes 0.000 claims description 26
- 239000003607 modifier Substances 0.000 claims description 26
- 101001001516 Homo sapiens Phosphatidylinositol 4-kinase alpha Proteins 0.000 claims description 23
- 102100036161 Phosphatidylinositol 4-kinase alpha Human genes 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 22
- 235000018417 cysteine Nutrition 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 21
- 102000001253 Protein Kinase Human genes 0.000 claims description 17
- 230000004048 modification Effects 0.000 claims description 17
- 238000012986 modification Methods 0.000 claims description 17
- 108060006633 protein kinase Proteins 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- XRKYMMUGXMWDAO-UHFFFAOYSA-N 2-(4-morpholinyl)-6-(1-thianthrenyl)-4-pyranone Chemical compound O1C(C=2C=3SC4=CC=CC=C4SC=3C=CC=2)=CC(=O)C=C1N1CCOCC1 XRKYMMUGXMWDAO-UHFFFAOYSA-N 0.000 claims description 15
- 239000012634 fragment Substances 0.000 claims description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 14
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 13
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 13
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 108091000080 Phosphotransferase Proteins 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 102000020233 phosphotransferase Human genes 0.000 claims description 9
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 claims description 8
- 102100036061 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Human genes 0.000 claims description 7
- 101710125691 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Proteins 0.000 claims description 7
- 101150097381 Mtor gene Proteins 0.000 claims description 6
- 210000004027 cell Anatomy 0.000 claims description 6
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 claims description 5
- 101710096503 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 claims description 5
- 239000013038 irreversible inhibitor Substances 0.000 claims description 5
- 239000000523 sample Substances 0.000 claims description 5
- 210000001519 tissue Anatomy 0.000 claims description 5
- DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical group N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 claims description 4
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 claims description 3
- 101710093328 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 claims description 3
- 102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 claims description 3
- 101710204747 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 claims description 3
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 51
- 125000004423 acyloxy group Chemical group 0.000 claims 10
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims 10
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims 10
- 239000012954 diazonium Substances 0.000 claims 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims 10
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 4
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims 4
- 239000006166 lysate Substances 0.000 claims 3
- 229960002685 biotin Drugs 0.000 claims 2
- 235000020958 biotin Nutrition 0.000 claims 2
- 239000011616 biotin Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000007850 fluorescent dye Substances 0.000 claims 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 229920000642 polymer Polymers 0.000 claims 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- 229920003169 water-soluble polymer Polymers 0.000 claims 2
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 208000035473 Communicable disease Diseases 0.000 claims 1
- 208000029462 Immunodeficiency disease Diseases 0.000 claims 1
- 230000006044 T cell activation Effects 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 239000012472 biological sample Substances 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 230000030833 cell death Effects 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 230000001066 destructive effect Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000003902 lesion Effects 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims 1
- 229960004072 thrombin Drugs 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 230000002427 irreversible effect Effects 0.000 abstract description 10
- 239000000126 substance Substances 0.000 abstract 1
- 150000002430 hydrocarbons Chemical group 0.000 description 89
- 102000038030 PI3Ks Human genes 0.000 description 78
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 53
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 50
- 125000004429 atom Chemical group 0.000 description 33
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 33
- 125000002757 morpholinyl group Chemical group 0.000 description 28
- 125000004193 piperazinyl group Chemical group 0.000 description 28
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 26
- 229910052799 carbon Inorganic materials 0.000 description 22
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 20
- 125000004043 oxo group Chemical group O=* 0.000 description 20
- 125000004076 pyridyl group Chemical group 0.000 description 19
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 18
- 125000003373 pyrazinyl group Chemical group 0.000 description 18
- 125000006850 spacer group Chemical group 0.000 description 18
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 18
- 125000003386 piperidinyl group Chemical group 0.000 description 17
- 125000000714 pyrimidinyl group Chemical group 0.000 description 17
- 125000005955 1H-indazolyl group Chemical group 0.000 description 16
- 125000005936 piperidyl group Chemical group 0.000 description 16
- 229930195734 saturated hydrocarbon Natural products 0.000 description 16
- 150000001413 amino acids Chemical group 0.000 description 15
- 125000004122 cyclic group Chemical group 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 13
- 238000004949 mass spectrometry Methods 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 125000005843 halogen group Chemical group 0.000 description 11
- 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 description 10
- 125000001041 indolyl group Chemical group 0.000 description 10
- 125000005750 substituted cyclic group Chemical group 0.000 description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 9
- 108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 9
- 102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 9
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 125000003003 spiro group Chemical group 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
- 125000001624 naphthyl group Chemical group 0.000 description 5
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 4
- 108010029190 1-Phosphatidylinositol 4-Kinase Proteins 0.000 description 4
- 102000001556 1-Phosphatidylinositol 4-Kinase Human genes 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 125000004419 alkynylene group Chemical group 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000013037 reversible inhibitor Substances 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical group C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 150000005005 aminopyrimidines Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 206010043189 Telangiectasia Diseases 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000002829 nitrogen Chemical class 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 208000009056 telangiectasis Diseases 0.000 description 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- QDITZBLZQQZVEE-YBEGLDIGSA-N (5z)-5-[(4-pyridin-4-ylquinolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C\C1=CC=C(N=CC=C2C=3C=CN=CC=3)C2=C1 QDITZBLZQQZVEE-YBEGLDIGSA-N 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- XAWPKHNOFIWWNZ-UHFFFAOYSA-N 1h-indol-6-ol Chemical compound OC1=CC=C2C=CNC2=C1 XAWPKHNOFIWWNZ-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 101710199605 Endoribonuclease Proteins 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100386053 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-3 gene Proteins 0.000 description 1
- 101100426732 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-9 gene Proteins 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 108091007999 druggable proteins Proteins 0.000 description 1
- 102000038037 druggable proteins Human genes 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001965 increasing effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000005545 phthalimidyl group Chemical group 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- HAMAGKWXRRTWCJ-UHFFFAOYSA-N pyrido[2,3-b][1,4]oxazin-3-one Chemical compound C1=CN=C2OC(=O)C=NC2=C1 HAMAGKWXRRTWCJ-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Oncology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Communicable Diseases (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24094709P | 2009-09-09 | 2009-09-09 | |
| US61/240,947 | 2009-09-09 | ||
| US37139610P | 2010-08-06 | 2010-08-06 | |
| US61/371,396 | 2010-08-06 | ||
| PCT/US2010/048317 WO2011031896A2 (en) | 2009-09-09 | 2010-09-09 | Pi3 kinase inhibitors and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2012110024A RU2012110024A (ru) | 2013-11-10 |
| RU2595718C2 true RU2595718C2 (ru) | 2016-08-27 |
Family
ID=43733099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2012110024/04A RU2595718C2 (ru) | 2009-09-09 | 2010-09-09 | Ингибиторы pi3-киназы и их применение |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20110230476A1 (enExample) |
| EP (1) | EP2475375A4 (enExample) |
| JP (1) | JP2013504325A (enExample) |
| KR (1) | KR20120063515A (enExample) |
| CN (1) | CN102625708A (enExample) |
| AU (1) | AU2010292198A1 (enExample) |
| BR (1) | BR112012008385A2 (enExample) |
| CA (1) | CA2773848A1 (enExample) |
| IL (1) | IL218555A0 (enExample) |
| MX (1) | MX339584B (enExample) |
| NZ (2) | NZ598808A (enExample) |
| PH (1) | PH12012500491A1 (enExample) |
| RU (1) | RU2595718C2 (enExample) |
| SG (2) | SG10201405598QA (enExample) |
| TW (2) | TW201609747A (enExample) |
| WO (1) | WO2011031896A2 (enExample) |
Families Citing this family (136)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101402474B1 (ko) * | 2006-04-26 | 2014-06-19 | 제넨테크, 인크. | 포스포이노시티드 3-키나제 억제제 화합물 및 이를 포함하는 약학적 조성물 |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| PL2300013T5 (pl) | 2008-05-21 | 2025-04-28 | Takeda Pharmaceutical Company Limited | Pochodne fosforu jako inhibitor kinazy |
| EP2478361A4 (en) | 2009-09-16 | 2014-05-21 | Celgene Avilomics Res Inc | CONJUGATES AND INHIBITORS OF PROTEIN KINASE |
| WO2011060321A1 (en) | 2009-11-16 | 2011-05-19 | Chdi, Inc. | Transglutaminase tg2 inhibitors, pharmaceutical compositions, and methods of use thereof |
| CN102812167A (zh) | 2009-12-30 | 2012-12-05 | 阿维拉制药公司 | 蛋白的配体-介导的共价修饰 |
| JP6130305B2 (ja) | 2011-02-23 | 2017-05-17 | インテリカイン, エルエルシー | キナーゼ阻害剤の組み合わせおよびそれらの使用 |
| US20120258967A1 (en) * | 2011-03-09 | 2012-10-11 | Avila Therapeutics, Inc. | Pi3 kinase inhibitors and uses thereof |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| WO2012154608A1 (en) * | 2011-05-06 | 2012-11-15 | Intellikine, Llc | Reactive mtor and pi3 kinase inhibitors and uses thereof |
| WO2012154610A1 (en) * | 2011-05-06 | 2012-11-15 | Intellikine, Llc | Reactive pi3k kinase inhibitors and uses thereof |
| US8889716B2 (en) | 2011-05-10 | 2014-11-18 | Chdi Foundation, Inc. | Transglutaminase TG2 inhibitors, pharmaceutical compositions, and methods of use thereof |
| AU2012283775A1 (en) | 2011-07-13 | 2014-01-23 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| MX342326B (es) | 2011-09-27 | 2016-09-26 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inhibidoras de idh mutante. |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| UY34632A (es) | 2012-02-24 | 2013-05-31 | Novartis Ag | Compuestos de oxazolidin- 2- ona y usos de los mismos |
| WO2013144180A1 (en) * | 2012-03-28 | 2013-10-03 | Intervet International B.V. | Heteroaryl compounds with cyclic bridging unit for use in the treatment helminth infection |
| US20150087628A1 (en) | 2012-04-10 | 2015-03-26 | The Regents Of The University Of California | Compositions and methods for treating cancer |
| US9879003B2 (en) | 2012-04-11 | 2018-01-30 | Dana-Farber Cancer Institute, Inc. | Host targeted inhibitors of dengue virus and other viruses |
| AU2013251475B2 (en) | 2012-04-26 | 2018-01-04 | The General Hospital Corporation | Agents and methods for treating and preventing seborrheic keratosis |
| JP6469567B2 (ja) | 2012-05-05 | 2019-02-13 | アリアド・ファーマシューティカルズ・インコーポレイテッド | Egfr発動性がんの細胞増殖阻害用化合物 |
| US20150204846A1 (en) * | 2012-05-15 | 2015-07-23 | New York University | Phosphatidylinositol-3-kinase c2 beta modulators and methods of use thereof |
| WO2014012093A1 (en) * | 2012-07-13 | 2014-01-16 | Wake Forest University Health Sciences | Prostate cancer targeted prodrugs and methods of use thereof |
| US9572811B2 (en) | 2012-08-03 | 2017-02-21 | Principia Biopharma Inc. | Treatment of dry eye |
| US11458199B2 (en) | 2012-08-21 | 2022-10-04 | Opko Pharmaceuticals, Llc | Liposome formulations |
| HUE058912T2 (hu) | 2012-08-21 | 2022-09-28 | Opko Pharmaceuticals Llc | Liposzóma készítmények |
| SMT201900344T1 (it) | 2012-09-10 | 2019-07-11 | Principia Biopharma Inc | Composti di pirazolopirimidina come inibitori di chinasi |
| US10000483B2 (en) | 2012-10-19 | 2018-06-19 | Dana-Farber Cancer Institute, Inc. | Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof |
| US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
| NZ708870A (en) | 2012-12-21 | 2016-09-30 | Gilead Calistoga Llc | Isoquinolinone or quinazolinone phosphatidylinositol 3-kinase inhibitors |
| JP6125663B2 (ja) | 2012-12-21 | 2017-05-10 | ギリアード カリストガ エルエルシー | ホスファチジルイノシトール3−キナーゼ阻害剤としての置換ピリミジンアミノアルキル−キナゾロン |
| WO2014130612A1 (en) * | 2013-02-20 | 2014-08-28 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| PE20151939A1 (es) | 2013-03-14 | 2016-01-08 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inhibidores de idh mutante |
| US10202356B2 (en) | 2013-03-14 | 2019-02-12 | Tolero Pharmaceuticals, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
| TW201524952A (zh) * | 2013-03-15 | 2015-07-01 | Araxes Pharma Llc | Kras g12c之共價抑制劑 |
| UY35464A (es) | 2013-03-15 | 2014-10-31 | Araxes Pharma Llc | Inhibidores covalentes de kras g12c. |
| CN105246482A (zh) * | 2013-03-15 | 2016-01-13 | 因特利凯有限责任公司 | 激酶抑制剂的组合及其用途 |
| US9745319B2 (en) | 2013-03-15 | 2017-08-29 | Araxes Pharma Llc | Irreversible covalent inhibitors of the GTPase K-Ras G12C |
| JP6378918B2 (ja) * | 2013-04-03 | 2018-08-22 | 株式会社ヤクルト本社 | チアゾリジン誘導体又はその塩を有効成分とするPim阻害剤 |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| MA42164B1 (fr) * | 2013-05-01 | 2019-12-31 | Hoffmann La Roche | Composes biheteroaryle et leurs utilisations |
| US10508309B2 (en) * | 2013-05-17 | 2019-12-17 | The General Hospital Corporation | Methods for detecting and treating variants of seborrheic keratoses |
| NZ714710A (en) | 2013-06-14 | 2016-11-25 | Gilead Sciences Inc | Phosphatidylinositol 3-kinase inhibitors |
| UY35675A (es) | 2013-07-24 | 2015-02-27 | Novartis Ag | Derivados sustituidos de quinazolin-4-ona |
| US9624224B2 (en) | 2013-09-30 | 2017-04-18 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| TWI659021B (zh) | 2013-10-10 | 2019-05-11 | 亞瑞克西斯製藥公司 | Kras g12c之抑制劑 |
| WO2015057655A1 (en) | 2013-10-14 | 2015-04-23 | Eisai R&D Management Co., Ltd. | Selectively substituted quinoline compounds |
| MD4635C1 (ro) | 2013-10-14 | 2020-01-31 | Eisai R&D Management Co., Ltd. | Compuşi de chinolină substituiţi selectiv |
| ES2676734T3 (es) * | 2013-10-18 | 2018-07-24 | Syros Pharmaceuticals, Inc. | Compuestos heteroatómicos útiles para el tratamiento de enfermedades proliferativas |
| AU2014352463B2 (en) * | 2013-11-20 | 2017-05-11 | Beijing Forelandpharma Co. Ltd. | Ketone derivatives of imidazoles, pharmaceutical combinations and uses thereof |
| KR102331833B1 (ko) | 2013-12-02 | 2021-11-25 | 케모센트릭스, 인크. | Ccr6 화합물 |
| KR20220027271A (ko) | 2014-02-21 | 2022-03-07 | 프린시피아 바이오파마, 인코퍼레이티드 | Btk 억제제의 염 및 고체 형태 |
| JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| US9862701B2 (en) | 2014-09-25 | 2018-01-09 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| WO2016049568A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Methods and compositions for inhibition of ras |
| CA2970723C (en) | 2014-12-18 | 2023-09-05 | Principia Biopharma Inc. | Treatment of pemphigus |
| RU2704826C2 (ru) * | 2014-12-24 | 2019-10-31 | Китер Бьотек С.Р.Л. | НОВЫЙ ПЕПТИД-ИНГИБИТОР PI3Kγ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ ОРГАНОВ ДЫХАНИЯ |
| EP3280708B1 (en) | 2015-04-10 | 2021-09-01 | Araxes Pharma LLC | Substituted quinazoline compounds and methods of use thereof |
| ES2856880T3 (es) | 2015-04-15 | 2021-09-28 | Araxes Pharma Llc | Inhibidores tricíclicos condensados de KRAS y métodos de uso de los mismos |
| WO2016172952A1 (zh) | 2015-04-30 | 2016-11-03 | 江苏挪贝肽医药科技有限公司 | PI4KIIIα蛋白及相关的膜蛋白复合体在治疗阿尔茨海默病中的应用 |
| EP3297629A1 (en) | 2015-05-20 | 2018-03-28 | Novartis AG | Pharmaceutical combination of everolimus with dactolisib |
| MA42242A (fr) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc | Inhibiteurs de la tyrosine kinase |
| US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
| US10647703B2 (en) | 2015-09-28 | 2020-05-12 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| US10858343B2 (en) | 2015-09-28 | 2020-12-08 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| WO2017058792A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| US10975071B2 (en) | 2015-09-28 | 2021-04-13 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| WO2017058807A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058902A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| US10730867B2 (en) | 2015-09-28 | 2020-08-04 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| EP3364977A4 (en) | 2015-10-19 | 2019-09-04 | Araxes Pharma LLC | PROCESS FOR SCREENING INHIBITORS OF RAS |
| EA038635B9 (ru) | 2015-11-16 | 2021-10-26 | Араксис Фарма Ллк | 2-замещенные соединения хиназолина, содержащие замещенную гетероциклическую группу, и способы их применения |
| US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
| RU2617694C1 (ru) * | 2015-12-24 | 2017-04-26 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | Амиды акриловой и метакриловой кислот с олигопиперидинами и способ их получения |
| RU2617409C1 (ru) * | 2015-12-24 | 2017-04-25 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | Амиды акриловой и метакриловой кислот с n-алкилпиперазино-пиперидинами и способ их получения |
| GB201602527D0 (en) * | 2016-02-12 | 2016-03-30 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
| US10822312B2 (en) | 2016-03-30 | 2020-11-03 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
| EP3464275B1 (en) | 2016-05-26 | 2024-05-08 | Recurium IP Holdings, LLC | Egfr inhibitor compounds |
| WO2018005849A1 (en) | 2016-06-29 | 2018-01-04 | Principia Biopharma Inc. | Modified release formulations of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
| WO2018002958A1 (en) | 2016-06-30 | 2018-01-04 | Sun Pharma Advanced Research Company Limited | Novel hydrazide containing compounds as btk inhibitors |
| US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
| TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| US10280172B2 (en) | 2016-09-29 | 2019-05-07 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| JP2019534260A (ja) | 2016-10-07 | 2019-11-28 | アラクセス ファーマ エルエルシー | Rasの阻害剤としての複素環式化合物およびその使用方法 |
| BR112019010470A2 (pt) | 2016-11-23 | 2019-09-10 | Novartis Ag | métodos de realce de resposta imune com everolimo, dactolisib ou ambos |
| CN106755343A (zh) * | 2016-12-01 | 2017-05-31 | 北京致成生物医学科技有限公司 | 胰腺癌预后诊断分子标记物 |
| WO2018140599A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Benzothiophene and benzothiazole compounds and methods of use thereof |
| WO2018140600A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Fused hetero-hetero bicyclic compounds and methods of use thereof |
| WO2018140512A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Fused bicyclic benzoheteroaromatic compounds and methods of use thereof |
| WO2018140514A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds as kras g12c inhibitors for the treatment of cancer |
| US11279689B2 (en) | 2017-01-26 | 2022-03-22 | Araxes Pharma Llc | 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1 yl)prop-2-en-1-one derivatives and similar compounds as KRAS G12C modulators for treating cancer |
| WO2018195649A1 (en) * | 2017-04-26 | 2018-11-01 | Alberta Research Chemicals Inc. | Substituted tetrahydropyridine derivatives as ido-1 inhibitors and uses thereof |
| CN110869357A (zh) | 2017-05-25 | 2020-03-06 | 亚瑞克西斯制药公司 | 化合物及其用于治疗癌症的使用方法 |
| US11639346B2 (en) | 2017-05-25 | 2023-05-02 | Araxes Pharma Llc | Quinazoline derivatives as modulators of mutant KRAS, HRAS or NRAS |
| AU2018271990A1 (en) | 2017-05-25 | 2019-12-12 | Araxes Pharma Llc | Covalent inhibitors of KRAS |
| US10596165B2 (en) | 2018-02-12 | 2020-03-24 | resTORbio, Inc. | Combination therapies |
| CA3096984A1 (en) | 2018-04-05 | 2019-10-10 | Sumitomo Dainippon Pharma Oncology, Inc. | Axl kinase inhibitors and use of the same |
| ES3032793T3 (en) | 2018-04-10 | 2025-07-24 | Neuropore Therapies Inc | Tri-substituted aryl and heteroaryl derivatives as modulators of pi3-kinase and autophagy pathways |
| ES2929292T3 (es) | 2018-04-10 | 2022-11-28 | Neuropore Therapies Inc | Derivados de morfolina como inhibidores de Vps34 |
| MX2021000977A (es) | 2018-07-26 | 2021-04-12 | Sumitomo Pharma Oncology Inc | Metodos para tratar enfermedades asociadas con expresion anormal de receptor de activina a tipo 1 (acvr1) e inhibidores de acvr1 para uso en los mismos. |
| US12134620B2 (en) * | 2018-08-01 | 2024-11-05 | Araxes Pharma Llc | Heterocyclic spiro compounds and methods of use thereof for the treatment of cancer |
| KR102328682B1 (ko) | 2018-08-27 | 2021-11-18 | 주식회사 대웅제약 | 신규한 헤테로사이클릭아민 유도체 및 이를 포함하는 약학 조성물 |
| EP3849545A1 (en) * | 2018-09-10 | 2021-07-21 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of neurofibromatosis |
| WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| EP3898626A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of fgfr tyrosine kinases |
| CN120789282A (zh) * | 2019-09-19 | 2025-10-17 | 托特斯医药公司 | 治疗性缀合物 |
| TWI877239B (zh) | 2019-10-14 | 2025-03-21 | 美商普林斯匹亞生物製藥公司 | 藉由投予(R)-2-[3-[4-胺基-3-(2-氟-4-苯氧基-苯基)吡唑并[3,4-d]嘧啶-1-基]哌啶-1-羰基]-4-甲基-4-[4-(氧呾-3-基)哌-1-基]戊-2-烯腈來治療免疫血小板減少症之方法 |
| EP4045485A1 (en) | 2019-10-18 | 2022-08-24 | The Regents Of The University Of California | 3-phenylsulphonyl-quinoline derivatives as agents for treating pathogenic blood vessels disorders |
| WO2021142252A1 (en) * | 2020-01-10 | 2021-07-15 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
| US11530218B2 (en) | 2020-01-20 | 2022-12-20 | Incyte Corporation | Spiro compounds as inhibitors of KRAS |
| BR112022014149A2 (pt) | 2020-01-22 | 2022-09-27 | Principia Biopharma Inc | Formas cristalinas de 2-[3-[4-amino-3-(2-fluoro-4-fenóxi-fenil)-1h-pirazolo[3,4-d]pirimidina-1-il]piperidina-1-carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il]pent-2-enenitrila |
| TWI874791B (zh) | 2020-02-18 | 2025-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| AR121356A1 (es) | 2020-02-18 | 2022-05-11 | Gilead Sciences Inc | Compuestos antivirales |
| TWI883391B (zh) | 2020-02-18 | 2025-05-11 | 美商基利科學股份有限公司 | 抗病毒化合物 |
| WO2021231526A1 (en) | 2020-05-13 | 2021-11-18 | Incyte Corporation | Fused pyrimidine compounds as kras inhibitors |
| WO2021242859A1 (en) * | 2020-05-27 | 2021-12-02 | Duke University | Compositions and methods for sensitizing acute myeloid leukemias to chemotherapy |
| WO2022047093A1 (en) | 2020-08-28 | 2022-03-03 | Incyte Corporation | Vinyl imidazole compounds as inhibitors of kras |
| WO2022072783A1 (en) | 2020-10-02 | 2022-04-07 | Incyte Corporation | Bicyclic dione compounds as inhibitors of kras |
| CN113045582B (zh) * | 2021-02-05 | 2022-12-23 | 中国药科大学 | Parp-1/pi3k双靶点抑制剂或其药学上可接受的盐及其制备方法与用途 |
| EP4308121A4 (en) * | 2021-03-18 | 2025-02-19 | Totus Medicines Inc. | THERAPEUTIC CONJUGATES |
| WO2022204112A1 (en) | 2021-03-22 | 2022-09-29 | Incyte Corporation | Imidazole and triazole kras inhibitors |
| CN117396470A (zh) * | 2021-04-09 | 2024-01-12 | 巴塞尔大学 | 作为pi3k的可逆和不可逆共价抑制剂的三嗪衍生物 |
| JP2024516361A (ja) * | 2021-04-09 | 2024-04-15 | ウニヴェアズィテート バーゼル | Pi3kの可逆的および不可逆的共有結合性阻害剤としてのトリアジン誘導体 |
| EP4323362B1 (en) | 2021-04-16 | 2025-05-07 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
| WO2023283213A1 (en) | 2021-07-07 | 2023-01-12 | Incyte Corporation | Tricyclic compounds as inhibitors of kras |
| TW202321191A (zh) * | 2021-07-29 | 2023-06-01 | 美商賽迪拉治療股份有限公司 | Tead抑制劑及其用途 |
| CA3228162A1 (en) | 2021-08-18 | 2023-02-23 | Gilead Sciences, Inc. | Phospholipid compounds and methods of making and using the same |
| CA3229855A1 (en) | 2021-08-31 | 2023-03-09 | Incyte Corporation | Naphthyridine compounds as inhibitors of kras |
| WO2023049697A1 (en) | 2021-09-21 | 2023-03-30 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of kras |
| CN113754680B (zh) * | 2021-09-28 | 2022-07-22 | 云白药征武科技(上海)有限公司 | 一种α氟代酰基哌嗪衍生物及其制备和应用 |
| WO2023056421A1 (en) | 2021-10-01 | 2023-04-06 | Incyte Corporation | Pyrazoloquinoline kras inhibitors |
| MX2024004444A (es) | 2021-10-14 | 2024-05-08 | Incyte Corp | Compuestos de quinolina como inhibidores de la proteina del virus de sarcoma de rata kirsten (kras). |
| WO2024182447A1 (en) * | 2023-02-28 | 2024-09-06 | Vividion Therapeutics, Inc. | Compounds and methods for modulating ras-pi3k |
| WO2025188658A1 (en) * | 2024-03-06 | 2025-09-12 | Alterome Therapeutics, Inc. | Akt1 modulators |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040266780A1 (en) * | 2000-04-25 | 2004-12-30 | Chanchal Sadhu | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| WO2006089106A2 (en) * | 2005-02-17 | 2006-08-24 | Icos Corporation | Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation |
| WO2008151183A1 (en) * | 2007-06-04 | 2008-12-11 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| RU2443706C2 (ru) * | 2006-04-26 | 2012-02-27 | Дженентек, Инк. | Фармацевтические соединения |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20131159B1 (hr) * | 2002-09-30 | 2019-11-01 | Bayer Ip Gmbh | Taljeni azol-pirimidin derivati |
| AR046845A1 (es) * | 2003-11-21 | 2005-12-28 | Novartis Ag | Derivados de 1h-imidazo[4,5-c]quinolina para tratamiento de enfermedades dependientes de las proteino-quinasas |
| RS55546B1 (sr) * | 2004-05-13 | 2017-05-31 | Icos Corp | Hinazolinoni kao inhibitori humane fosfatidilonozitol 3-delta kinaze |
| JO2660B1 (en) * | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| KR101402474B1 (ko) * | 2006-04-26 | 2014-06-19 | 제넨테크, 인크. | 포스포이노시티드 3-키나제 억제제 화합물 및 이를 포함하는 약학적 조성물 |
| GB0611152D0 (en) * | 2006-06-06 | 2006-07-19 | Ucb Sa | Therapeutic agents |
| DK2050749T3 (en) * | 2006-08-08 | 2018-01-08 | Chugai Pharmaceutical Co Ltd | PYRIMIDINE DERIVATIVES AS PI3K INHIBITOR AND USE THEREOF |
| US20080234262A1 (en) * | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| PE20090717A1 (es) * | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
| CA2699202C (en) * | 2007-09-12 | 2016-09-27 | F. Hoffmann-La Roche Ag | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents, and methods of use |
| US8354528B2 (en) * | 2007-10-25 | 2013-01-15 | Genentech, Inc. | Process for making thienopyrimidine compounds |
| GB0805818D0 (en) * | 2008-03-31 | 2008-04-30 | Ucb Pharma Sa | Therapeutic agents |
| EA024252B1 (ru) * | 2009-01-08 | 2016-08-31 | Кьюрис, Инк. | Ингибиторы фосфоинозитид-3-киназ с цинксвязывающей группой |
-
2010
- 2010-09-09 JP JP2012528906A patent/JP2013504325A/ja active Pending
- 2010-09-09 SG SG10201405598QA patent/SG10201405598QA/en unknown
- 2010-09-09 TW TW104118050A patent/TW201609747A/zh unknown
- 2010-09-09 PH PH1/2012/500491A patent/PH12012500491A1/en unknown
- 2010-09-09 NZ NZ598808A patent/NZ598808A/en not_active IP Right Cessation
- 2010-09-09 KR KR1020127009074A patent/KR20120063515A/ko not_active Ceased
- 2010-09-09 NZ NZ626650A patent/NZ626650A/en not_active IP Right Cessation
- 2010-09-09 US US12/878,965 patent/US20110230476A1/en not_active Abandoned
- 2010-09-09 BR BR112012008385A patent/BR112012008385A2/pt not_active IP Right Cessation
- 2010-09-09 EP EP10816104A patent/EP2475375A4/en not_active Ceased
- 2010-09-09 TW TW099130780A patent/TWI499592B/zh not_active IP Right Cessation
- 2010-09-09 WO PCT/US2010/048317 patent/WO2011031896A2/en not_active Ceased
- 2010-09-09 RU RU2012110024/04A patent/RU2595718C2/ru not_active IP Right Cessation
- 2010-09-09 CA CA2773848A patent/CA2773848A1/en not_active Abandoned
- 2010-09-09 AU AU2010292198A patent/AU2010292198A1/en not_active Abandoned
- 2010-09-09 MX MX2012002972A patent/MX339584B/es active IP Right Grant
- 2010-09-09 CN CN201080048947XA patent/CN102625708A/zh active Pending
- 2010-09-09 SG SG2012016960A patent/SG179085A1/en unknown
-
2012
- 2012-03-08 IL IL218555A patent/IL218555A0/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040266780A1 (en) * | 2000-04-25 | 2004-12-30 | Chanchal Sadhu | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| WO2006089106A2 (en) * | 2005-02-17 | 2006-08-24 | Icos Corporation | Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation |
| RU2443706C2 (ru) * | 2006-04-26 | 2012-02-27 | Дженентек, Инк. | Фармацевтические соединения |
| WO2008151183A1 (en) * | 2007-06-04 | 2008-12-11 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
Non-Patent Citations (1)
Also Published As
| Publication number | Publication date |
|---|---|
| CN102625708A (zh) | 2012-08-01 |
| SG179085A1 (en) | 2012-04-27 |
| RU2012110024A (ru) | 2013-11-10 |
| CA2773848A1 (en) | 2011-03-17 |
| JP2013504325A (ja) | 2013-02-07 |
| MX2012002972A (es) | 2012-06-25 |
| TWI499592B (zh) | 2015-09-11 |
| NZ598808A (en) | 2014-07-25 |
| TW201120047A (en) | 2011-06-16 |
| EP2475375A2 (en) | 2012-07-18 |
| SG10201405598QA (en) | 2014-11-27 |
| US20110230476A1 (en) | 2011-09-22 |
| NZ626650A (en) | 2015-12-24 |
| TW201609747A (zh) | 2016-03-16 |
| KR20120063515A (ko) | 2012-06-15 |
| AU2010292198A1 (en) | 2012-04-05 |
| EP2475375A4 (en) | 2013-02-20 |
| IL218555A0 (en) | 2012-05-31 |
| PH12012500491A1 (en) | 2018-03-21 |
| WO2011031896A3 (en) | 2011-05-12 |
| MX339584B (es) | 2016-06-01 |
| WO2011031896A2 (en) | 2011-03-17 |
| BR112012008385A2 (pt) | 2019-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2595718C2 (ru) | Ингибиторы pi3-киназы и их применение | |
| AU2012225382B2 (en) | PI3 kinase inhibitors and uses thereof | |
| JP7530360B2 (ja) | Tyk2阻害剤およびその使用 | |
| JP7699052B2 (ja) | Tyk2阻害剤およびその使用 | |
| JP2015528801A (ja) | Irak阻害剤およびその使用 | |
| CN105142639A (zh) | Irak抑制剂和其用途 | |
| CN106232122A (zh) | Irak抑制剂和其用途 | |
| KR20130031234A (ko) | 헤테로사이클릭 화합물 및 이의 용도 | |
| TW200911810A (en) | Substituted imidazopyridazines and pyrrolopyrimidines as lipid kinase inhibitors | |
| AU2012310168B2 (en) | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase | |
| WO2014011911A2 (en) | Irak inhibitors and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HZ9A | Changing address for correspondence with an applicant | ||
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20150520 |
|
| FZ9A | Application not withdrawn (correction of the notice of withdrawal) |
Effective date: 20150709 |
|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20170910 |