ES2911040T3 - Nuevos derivados de heteroaril amida como inhibidores selectivos de histona deacetilasa 1 y 2 (HDAC1/2) - Google Patents
Nuevos derivados de heteroaril amida como inhibidores selectivos de histona deacetilasa 1 y 2 (HDAC1/2) Download PDFInfo
- Publication number
- ES2911040T3 ES2911040T3 ES18789777T ES18789777T ES2911040T3 ES 2911040 T3 ES2911040 T3 ES 2911040T3 ES 18789777 T ES18789777 T ES 18789777T ES 18789777 T ES18789777 T ES 18789777T ES 2911040 T3 ES2911040 T3 ES 2911040T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- amino
- pyridin
- fluorophenyl
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- -1 heteroaryl amide Chemical class 0.000 title claims description 37
- 102100039999 Histone deacetylase 2 Human genes 0.000 title abstract description 79
- 108010023981 Histone Deacetylase 2 Proteins 0.000 title abstract description 78
- 102100039996 Histone deacetylase 1 Human genes 0.000 title abstract description 63
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 title abstract description 57
- 229940124639 Selective inhibitor Drugs 0.000 title abstract description 10
- 108010024124 Histone Deacetylase 1 Proteins 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 83
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
- 238000011282 treatment Methods 0.000 claims abstract description 34
- 201000011510 cancer Diseases 0.000 claims abstract description 29
- 201000010099 disease Diseases 0.000 claims abstract description 21
- 206010019280 Heart failures Diseases 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 16
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
- 208000030761 polycystic kidney disease Diseases 0.000 claims abstract description 10
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims abstract description 8
- 208000006029 Cardiomegaly Diseases 0.000 claims abstract description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 7
- 208000007056 sickle cell anemia Diseases 0.000 claims abstract description 7
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 6
- 230000001575 pathological effect Effects 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 18
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 13
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 208000005017 glioblastoma Diseases 0.000 claims description 10
- 208000007538 neurilemmoma Diseases 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 8
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 8
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 229960004964 temozolomide Drugs 0.000 claims description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 7
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 7
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 7
- 206010029260 Neuroblastoma Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 claims description 7
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 7
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 7
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 229940127089 cytotoxic agent Drugs 0.000 claims description 7
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 claims description 7
- 201000005962 mycosis fungoides Diseases 0.000 claims description 7
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 7
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 6
- 208000034578 Multiple myelomas Diseases 0.000 claims description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
- 208000002903 Thalassemia Diseases 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 231100000419 toxicity Toxicity 0.000 claims description 6
- 230000001988 toxicity Effects 0.000 claims description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 5
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 5
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims description 5
- 206010003571 Astrocytoma Diseases 0.000 claims description 5
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 5
- PYVZAFAYVRKMEG-UHFFFAOYSA-N CN1CCN(CCNc2ccc(cn2)C(=O)Nc2nc(ccc2N)-c2ccc(F)cc2)CC1 Chemical compound CN1CCN(CCNc2ccc(cn2)C(=O)Nc2nc(ccc2N)-c2ccc(F)cc2)CC1 PYVZAFAYVRKMEG-UHFFFAOYSA-N 0.000 claims description 5
- 208000009798 Craniopharyngioma Diseases 0.000 claims description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 5
- 206010014967 Ependymoma Diseases 0.000 claims description 5
- 201000004066 Ganglioglioma Diseases 0.000 claims description 5
- 208000032612 Glial tumor Diseases 0.000 claims description 5
- 206010018338 Glioma Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 208000000172 Medulloblastoma Diseases 0.000 claims description 5
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 5
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 210000001072 colon Anatomy 0.000 claims description 5
- 239000013066 combination product Substances 0.000 claims description 5
- 229940127555 combination product Drugs 0.000 claims description 5
- 229960004397 cyclophosphamide Drugs 0.000 claims description 5
- 206010013663 drug dependence Diseases 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 5
- 239000003018 immunosuppressive agent Substances 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 206010027191 meningioma Diseases 0.000 claims description 5
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 5
- 150000003431 steroids Chemical class 0.000 claims description 5
- 201000011549 stomach cancer Diseases 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 102100032187 Androgen receptor Human genes 0.000 claims description 4
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims description 4
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 4
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 claims description 4
- 208000027747 Kennedy disease Diseases 0.000 claims description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 4
- 206010068871 Myotonic dystrophy Diseases 0.000 claims description 4
- 208000025317 T-cell and NK-cell neoplasm Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 229960005243 carmustine Drugs 0.000 claims description 4
- 201000007455 central nervous system cancer Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229960005420 etoposide Drugs 0.000 claims description 4
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- 229960002621 pembrolizumab Drugs 0.000 claims description 4
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 claims description 4
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 4
- 229960004528 vincristine Drugs 0.000 claims description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 4
- 102000014461 Ataxins Human genes 0.000 claims description 3
- 108010078286 Ataxins Proteins 0.000 claims description 3
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 3
- IMTKNPIMLAUFLM-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-(2-pyridin-3-ylethylamino)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)NCCC=1C=NC=CC=1)=O IMTKNPIMLAUFLM-UHFFFAOYSA-N 0.000 claims description 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 3
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 3
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 claims description 3
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
- 229960004562 carboplatin Drugs 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 239000002955 immunomodulating agent Substances 0.000 claims description 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 3
- 229960004768 irinotecan Drugs 0.000 claims description 3
- 229960002247 lomustine Drugs 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 229960003301 nivolumab Drugs 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 229950009791 durvalumab Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 229960005386 ipilimumab Drugs 0.000 claims description 2
- 229950010773 pidilizumab Drugs 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 229950007217 tremelimumab Drugs 0.000 claims description 2
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims 1
- MIKMTIHPFGCBQQ-UHFFFAOYSA-N NC=1C(=NC(=CC1)C1=CC=CC=C1)NC(=O)C=1C=NC(=NC1)N1CCN(CC1)C.NC=1C(=NC(=CC1)C1=CC(=C(C=C1)F)F)NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O Chemical compound NC=1C(=NC(=CC1)C1=CC=CC=C1)NC(=O)C=1C=NC(=NC1)N1CCN(CC1)C.NC=1C(=NC(=CC1)C1=CC(=C(C=C1)F)F)NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O MIKMTIHPFGCBQQ-UHFFFAOYSA-N 0.000 claims 1
- 102000003964 Histone deacetylase Human genes 0.000 abstract description 74
- 108090000353 Histone deacetylase Proteins 0.000 abstract description 74
- 230000005764 inhibitory process Effects 0.000 abstract description 26
- 238000000034 method Methods 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 101001035011 Homo sapiens Histone deacetylase 2 Proteins 0.000 abstract 1
- 206010043391 Thalassaemia beta Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 230000015572 biosynthetic process Effects 0.000 description 47
- 238000003786 synthesis reaction Methods 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 35
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 31
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- 239000010410 layer Substances 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 230000014509 gene expression Effects 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000000203 mixture Substances 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 239000003112 inhibitor Substances 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 150000008064 anhydrides Chemical class 0.000 description 14
- 210000003169 central nervous system Anatomy 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 12
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 8
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
- 230000021736 acetylation Effects 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 102100021455 Histone deacetylase 3 Human genes 0.000 description 5
- 108010033040 Histones Proteins 0.000 description 5
- 101000899282 Homo sapiens Histone deacetylase 3 Proteins 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 5
- 229960001467 bortezomib Drugs 0.000 description 5
- 210000004081 cilia Anatomy 0.000 description 5
- 230000001973 epigenetic effect Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 102000012195 Fructose-1,6-bisphosphatases Human genes 0.000 description 4
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 4
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 description 4
- 108010044467 Isoenzymes Proteins 0.000 description 4
- NAYYYJOGCAOLJY-UHFFFAOYSA-N NC1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1ccc(F)cc1 Chemical compound NC1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1ccc(F)cc1 NAYYYJOGCAOLJY-UHFFFAOYSA-N 0.000 description 4
- KHEIHESTTQFPKT-UHFFFAOYSA-N NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1CC1)=O Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1CC1)=O KHEIHESTTQFPKT-UHFFFAOYSA-N 0.000 description 4
- VOIHKLVJHPTOJG-UHFFFAOYSA-N Nc1ccc(nc1NC(=O)c1ccc(nc1)N1CCNCC1)-c1ccc(F)cc1 Chemical compound Nc1ccc(nc1NC(=O)c1ccc(nc1)N1CCNCC1)-c1ccc(F)cc1 VOIHKLVJHPTOJG-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 238000006640 acetylation reaction Methods 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000008499 blood brain barrier function Effects 0.000 description 4
- 210000001218 blood-brain barrier Anatomy 0.000 description 4
- 210000005103 brain tumor initiating cell Anatomy 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000002018 overexpression Effects 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229910052725 zinc Inorganic materials 0.000 description 4
- 239000011701 zinc Substances 0.000 description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 208000015943 Coeliac disease Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 108010044495 Fetal Hemoglobin Proteins 0.000 description 3
- 208000001914 Fragile X syndrome Diseases 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 102100022537 Histone deacetylase 6 Human genes 0.000 description 3
- 101000899330 Homo sapiens Histone deacetylase 6 Proteins 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 description 3
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 238000010256 biochemical assay Methods 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 230000004641 brain development Effects 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 208000037906 ischaemic injury Diseases 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 229950006238 nadide Drugs 0.000 description 3
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- ICSNLGPSRYBMBD-CDYZYAPPSA-N pyridin-2-amine Chemical class NC1=CC=CC=[15N]1 ICSNLGPSRYBMBD-CDYZYAPPSA-N 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003826 tablet Substances 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
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- JCSQASXNPSZRIY-UHFFFAOYSA-N 2-chloro-N-(3-nitropyridin-2-yl)pyrimidine-5-carboxamide Chemical class ClC1=NC=C(C=N1)C(=O)NC1=NC=CC=C1[N+](=O)[O-] JCSQASXNPSZRIY-UHFFFAOYSA-N 0.000 description 2
- QHOINBKBMJLHPY-UHFFFAOYSA-N 2-chloroethyl formate Chemical compound ClCCOC=O QHOINBKBMJLHPY-UHFFFAOYSA-N 0.000 description 2
- NCWQLHHDGDXIJN-UHFFFAOYSA-N 6-(2-chloro-6-methylpyridin-4-yl)-5-(4-fluorophenyl)-1,2,4-triazin-3-amine Chemical compound ClC1=NC(C)=CC(C=2C(=NC(N)=NN=2)C=2C=CC(F)=CC=2)=C1 NCWQLHHDGDXIJN-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 108010074708 B7-H1 Antigen Proteins 0.000 description 2
- 102000036365 BRCA1 Human genes 0.000 description 2
- 108700020463 BRCA1 Proteins 0.000 description 2
- 101150072950 BRCA1 gene Proteins 0.000 description 2
- HOYMTUCTXPSEPI-UHFFFAOYSA-N CN1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1ccccc1 Chemical compound CN1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1ccccc1 HOYMTUCTXPSEPI-UHFFFAOYSA-N 0.000 description 2
- ZETOGDCIFTXONW-UHFFFAOYSA-N CN1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1cccs1 Chemical compound CN1CCN(CC1)c1ccc(cn1)C(=O)Nc1nc(ccc1N)-c1cccs1 ZETOGDCIFTXONW-UHFFFAOYSA-N 0.000 description 2
- LZIWZTUGGBAPRN-UHFFFAOYSA-N CN1CCN(CC1)c1ncc(cn1)C(=O)Nc1nc(ccc1N)-c1ccccc1 Chemical compound CN1CCN(CC1)c1ncc(cn1)C(=O)Nc1nc(ccc1N)-c1ccccc1 LZIWZTUGGBAPRN-UHFFFAOYSA-N 0.000 description 2
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102100031785 Endothelial transcription factor GATA-2 Human genes 0.000 description 2
- 108091005772 HDAC11 Proteins 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 102100039385 Histone deacetylase 11 Human genes 0.000 description 2
- 102100021454 Histone deacetylase 4 Human genes 0.000 description 2
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 2
- 102000006947 Histones Human genes 0.000 description 2
- 101001066265 Homo sapiens Endothelial transcription factor GATA-2 Proteins 0.000 description 2
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 description 2
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 241001077868 Joanna Species 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 description 2
- HEDRLXAJELJQMX-UHFFFAOYSA-N N-(3-amino-6-phenylpyridin-2-yl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=CC=C1)NC(C1=CN=C(C=C1)N1CCOCC1)=O HEDRLXAJELJQMX-UHFFFAOYSA-N 0.000 description 2
- LMDIRYFCVLIUBS-UHFFFAOYSA-N N-(3-amino-6-phenylpyridin-2-yl)pyridine-3-carboxamide Chemical compound C(C1=CN=CC=C1)(=O)NC1=NC(=CC=C1N)C1=CC=CC=C1 LMDIRYFCVLIUBS-UHFFFAOYSA-N 0.000 description 2
- XSDKKYWQAMJOOX-UHFFFAOYSA-N N-(3-amino-6-phenylpyridin-2-yl)pyrimidine-5-carboxamide Chemical compound N1=CN=CC(=C1)C(=O)NC1=NC(=CC=C1N)C1=CC=CC=C1 XSDKKYWQAMJOOX-UHFFFAOYSA-N 0.000 description 2
- NVAINNSHXUVIRG-UHFFFAOYSA-N N-(3-amino-6-pyridin-4-ylpyridin-2-yl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound NC=1C=CC(=NC=1NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O)C1=CC=NC=C1 NVAINNSHXUVIRG-UHFFFAOYSA-N 0.000 description 2
- PKXFRKZSOCWWEB-UHFFFAOYSA-N N-[3-amino-6-(3,4-difluorophenyl)pyridin-2-yl]-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC(=C(C=C1)F)F)NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O PKXFRKZSOCWWEB-UHFFFAOYSA-N 0.000 description 2
- IGOULBPDHSZBFS-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(=O)C=1C=NC(=NC=1)N1CCN(CC1)C IGOULBPDHSZBFS-UHFFFAOYSA-N 0.000 description 2
- STMDVAPHVHSTPD-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-2-(cyclopropylamino)pyrimidine-5-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(=O)C=1C=NC(=NC=1)NC1CC1 STMDVAPHVHSTPD-UHFFFAOYSA-N 0.000 description 2
- XKDWOGOLXPJYDY-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-2-morpholin-4-ylpyrimidine-5-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(=O)C=1C=NC(=NC=1)N1CCOCC1 XKDWOGOLXPJYDY-UHFFFAOYSA-N 0.000 description 2
- GJSKGWISSUKSKI-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-(3-cyanophenyl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1=CC(=CC=C1)C#N)=O GJSKGWISSUKSKI-UHFFFAOYSA-N 0.000 description 2
- LBENFYBFWNXKGL-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-(4-fluorophenyl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1=CC=C(C=C1)F)=O LBENFYBFWNXKGL-UHFFFAOYSA-N 0.000 description 2
- TUVFSLMAKAPSFZ-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O TUVFSLMAKAPSFZ-UHFFFAOYSA-N 0.000 description 2
- GFIVYKYFGAHRTQ-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)N1CCOCC1)=O GFIVYKYFGAHRTQ-UHFFFAOYSA-N 0.000 description 2
- FRGLYRMTPORECM-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-pyridin-3-ylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(=O)C=1C=CC(=NC=1)C=1C=NC=CC=1 FRGLYRMTPORECM-UHFFFAOYSA-N 0.000 description 2
- CSJVLRGRRWVFLQ-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-pyridin-4-ylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(=O)C=1C=CC(=NC=1)C1=CC=NC=C1 CSJVLRGRRWVFLQ-UHFFFAOYSA-N 0.000 description 2
- MIIPSBHLYOYGBT-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]pyridine-3-carboxamide Chemical compound C(C1=CN=CC=C1)(=O)NC1=NC(=CC=C1N)C1=CC=C(C=C1)F MIIPSBHLYOYGBT-UHFFFAOYSA-N 0.000 description 2
- GVYBRBWBTXMOFD-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]pyrimidine-5-carboxamide Chemical compound N1=CN=CC(=C1)C(=O)NC1=NC(=CC=C1N)C1=CC=C(C=C1)F GVYBRBWBTXMOFD-UHFFFAOYSA-N 0.000 description 2
- YZSBKRYCQIFMQF-UHFFFAOYSA-N N-[3-amino-6-(4-methoxyphenyl)pyridin-2-yl]-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)OC)NC(C1=CN=C(C=C1)N1CCN(CC1)C)=O YZSBKRYCQIFMQF-UHFFFAOYSA-N 0.000 description 2
- YSOFWCMPXKNRQK-UHFFFAOYSA-N N-[5-amino-2-(4-fluorophenyl)pyrimidin-4-yl]-6-(4-aminopiperidin-1-yl)pyridine-3-carboxamide Chemical compound NC=1C(=NC(=NC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)N1CCC(CC1)N)=O YSOFWCMPXKNRQK-UHFFFAOYSA-N 0.000 description 2
- RSFAENBIKFCFMN-UHFFFAOYSA-N N-[5-amino-2-(4-fluorophenyl)pyrimidin-4-yl]-6-piperazin-1-ylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=NC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)N1CCNCC1)=O RSFAENBIKFCFMN-UHFFFAOYSA-N 0.000 description 2
- CHVSPTIKEMVVJU-UHFFFAOYSA-N NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1=CC=CC=C1)=O Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1=CC=CC=C1)=O CHVSPTIKEMVVJU-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- ZZTPXXDOWPKSMC-UHFFFAOYSA-N Nc1ccc(nc1NC(=O)c1cnc(NC2CC2)nc1)-c1ccccc1 Chemical compound Nc1ccc(nc1NC(=O)c1cnc(NC2CC2)nc1)-c1ccccc1 ZZTPXXDOWPKSMC-UHFFFAOYSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 108010068097 Rad51 Recombinase Proteins 0.000 description 2
- 102000002490 Rad51 Recombinase Human genes 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940045799 anthracyclines and related substance Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003659 bee venom Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000007278 cognition impairment Effects 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 229960000684 cytarabine Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 229960001193 diclofenac sodium Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000006806 disease prevention Effects 0.000 description 2
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 description 2
- 229950005837 entinostat Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 230000001969 hypertrophic effect Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 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
- 230000007246 mechanism Effects 0.000 description 2
- 229950007812 mocetinostat Drugs 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- HORXBWNTEDOVKN-UHFFFAOYSA-N n-[[4-(4-phenyl-1,3-thiazol-2-yl)oxan-4-yl]methyl]-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide Chemical compound O1C(C(F)(F)F)=NC(C=2C=C(C=CC=2)C(=O)NCC2(CCOCC2)C=2SC=C(N=2)C=2C=CC=CC=2)=N1 HORXBWNTEDOVKN-UHFFFAOYSA-N 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 108010040003 polyglutamine Proteins 0.000 description 2
- 229920000155 polyglutamine Polymers 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000003207 proteasome inhibitor Substances 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 230000020341 sensory perception of pain Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- KNCHTBNNSQSLRV-YFKPBYRVSA-N (2s)-6-amino-2-[(2,2,2-trifluoroacetyl)amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)C(F)(F)F KNCHTBNNSQSLRV-YFKPBYRVSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- UBPALQIWOBFWQZ-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)-N-(3-nitro-6-phenylpyridin-2-yl)pyrimidine-5-carboxamide Chemical compound N1(C)CCN(CC1)C1=NC=C(C(=O)NC2=C(C=CC(C3=CC=CC=C3)=N2)N(=O)=O)C=N1 UBPALQIWOBFWQZ-UHFFFAOYSA-N 0.000 description 1
- CPFAOKFWFGXGIK-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethyldiazene Chemical compound CN1CCN(CC1)CCN=N CPFAOKFWFGXGIK-UHFFFAOYSA-N 0.000 description 1
- AENNZVJFCZSYOS-UHFFFAOYSA-N 2-(cyclopropylamino)-N-(3-nitro-6-phenylpyridin-2-yl)pyrimidine-5-carboxamide Chemical compound C1(=CN=C(N=C1)NC1CC1)C(=O)NC1=C(C=CC(C2=CC=CC=C2)=N1)N(=O)=O AENNZVJFCZSYOS-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- KDTYRKYOLSDHAZ-UHFFFAOYSA-N 2-chloro-N-(3-nitro-6-phenylpyridin-2-yl)pyrimidine-5-carboxamide Chemical compound N1=C(N=CC(=C1)C(=O)NC1=C(C=CC(C2=CC=CC=C2)=N1)N(=O)=O)Cl KDTYRKYOLSDHAZ-UHFFFAOYSA-N 0.000 description 1
- DUCXUPKLVVSJKA-UHFFFAOYSA-N 2-chloropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)N=C1 DUCXUPKLVVSJKA-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- PYSICVOJSJMFKP-UHFFFAOYSA-N 3,5-dibromo-2-chloropyridine Chemical compound ClC1=NC=C(Br)C=C1Br PYSICVOJSJMFKP-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- XBWMSLRYGXSAKH-UHFFFAOYSA-N 3-nitro-6-phenylpyridin-2-amine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(C=2C=CC=CC=2)=C1 XBWMSLRYGXSAKH-UHFFFAOYSA-N 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- JDBICVCLMHJJJN-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]pyridine-3-carboxamide Chemical compound N1(CCC(CC1)N)C1=NC=C(C(=O)NC2=C(C=CC(=N2)C2=CC=C(F)C=C2)N(=O)=O)C=C1 JDBICVCLMHJJJN-UHFFFAOYSA-N 0.000 description 1
- RFIPCMCYEWAOTP-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-N-(3-nitro-6-phenylpyridin-2-yl)pyridine-3-carboxamide Chemical compound CN1CCN(CC1)C1=NC=C(C(=O)NC2=NC(=CC=C2[N+](=O)[O-])C2=CC=CC=C2)C=C1 RFIPCMCYEWAOTP-UHFFFAOYSA-N 0.000 description 1
- UVBLRAZOKUKQFI-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)-N-(3-nitro-6-thiophen-2-ylpyridin-2-yl)pyridine-3-carboxamide Chemical compound C1N(CCN(C1)C)C1=CC=C(C=N1)C(=O)NC1=C(C=CC(=N1)C1=CC=CS1)N(=O)=O UVBLRAZOKUKQFI-UHFFFAOYSA-N 0.000 description 1
- WERABQRUGJIMKQ-UHFFFAOYSA-N 6-chloro-3-nitropyridin-2-amine Chemical compound NC1=NC(Cl)=CC=C1[N+]([O-])=O WERABQRUGJIMKQ-UHFFFAOYSA-N 0.000 description 1
- UCMBWEUEYQBDGX-UHFFFAOYSA-N 6-chloro-N-(3-nitro-6-phenylpyridin-2-yl)pyridine-3-carboxamide Chemical compound N1=C(C=CC(=C1)C(=O)NC1=C(C=CC(C2=CC=CC=C2)=N1)N(=O)=O)Cl UCMBWEUEYQBDGX-UHFFFAOYSA-N 0.000 description 1
- DFAZFUMIFHJGKL-UHFFFAOYSA-N 6-chloro-N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]pyridine-3-carboxamide Chemical compound C(=O)(C1=CN=C(Cl)C=C1)NC1=C(C=CC(C2=CC=C(F)C=C2)=N1)N(=O)=O DFAZFUMIFHJGKL-UHFFFAOYSA-N 0.000 description 1
- YZSICNRDDIFTGE-UHFFFAOYSA-N 6-cyclopentylpyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1C1CCCC1 YZSICNRDDIFTGE-UHFFFAOYSA-N 0.000 description 1
- MRYYYKVOJNQWKK-UHFFFAOYSA-N 6-cyclopropyl-N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]pyridine-3-carboxamide Chemical compound C1=CC(=CC=C1C1=CC=C(N(=O)=O)C(NC(=O)C2=CN=C(C=C2)C2CC2)=N1)F MRYYYKVOJNQWKK-UHFFFAOYSA-N 0.000 description 1
- DLFLQXUYRFIFOK-UHFFFAOYSA-N 6-phenylpyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 DLFLQXUYRFIFOK-UHFFFAOYSA-N 0.000 description 1
- KURQKNMKCGYWRJ-HNNXBMFYSA-N 7-(5-methylfuran-2-yl)-3-[[6-[[(3s)-oxolan-3-yl]oxymethyl]pyridin-2-yl]methyl]triazolo[4,5-d]pyrimidin-5-amine Chemical compound O1C(C)=CC=C1C1=NC(N)=NC2=C1N=NN2CC1=CC=CC(CO[C@@H]2COCC2)=N1 KURQKNMKCGYWRJ-HNNXBMFYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 102000014161 Aminohydrolases Human genes 0.000 description 1
- 108010011527 Aminohydrolases Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 101150017888 Bcl2 gene Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000005483 Cell Cycle Proteins Human genes 0.000 description 1
- 108010031896 Cell Cycle Proteins Proteins 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 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
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000012623 DNA damaging agent Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 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
- 230000010190 G1 phase Effects 0.000 description 1
- 102100021453 Histone deacetylase 5 Human genes 0.000 description 1
- 101710100812 Histone deacetylase HDAC1 Proteins 0.000 description 1
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 1
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 description 1
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 description 1
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 description 1
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 1
- 101001035694 Homo sapiens Polyamine deacetylase HDAC10 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 206010072877 Intestinal fibrosis Diseases 0.000 description 1
- 208000000913 Kidney Calculi Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 102000004855 Multi drug resistance-associated proteins Human genes 0.000 description 1
- 108090001099 Multi drug resistance-associated proteins Proteins 0.000 description 1
- 102000014842 Multidrug resistance proteins Human genes 0.000 description 1
- 108050005144 Multidrug resistance proteins Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MYRZOHWTGMJCQU-UHFFFAOYSA-N N-(3-aminopyridin-2-yl)pyridine-3-carboxamide Chemical class Nc1cccnc1NC(=O)c1cccnc1 MYRZOHWTGMJCQU-UHFFFAOYSA-N 0.000 description 1
- XFUXSADHHMASLB-UHFFFAOYSA-N N-[3-amino-6-(4-fluorophenyl)pyridin-2-yl]-6-cyclopentylpyridine-3-carboxamide Chemical compound NC=1C(=NC(=CC=1)C1=CC=C(C=C1)F)NC(C1=CN=C(C=C1)C1CCCC1)=O XFUXSADHHMASLB-UHFFFAOYSA-N 0.000 description 1
- JKLQYXBXZQZLJM-UHFFFAOYSA-N N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]-6-[2-(4-methylpiperazin-1-yl)ethylamino]pyridine-3-carboxamide Chemical compound C1=C(C(=O)NC2=C(C=CC(=N2)C2=CC=C(F)C=C2)N(=O)=O)C=NC(=C1)NCCN1CCN(CC1)C JKLQYXBXZQZLJM-UHFFFAOYSA-N 0.000 description 1
- RUHHYAMDNSRXTL-UHFFFAOYSA-N N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]-6-phenylpyridine-3-carboxamide Chemical compound FC1=CC=C(C=C1)C1=CC=C(C(=N1)NC(C1=CN=C(C=C1)C1=CC=CC=C1)=O)[N+](=O)[O-] RUHHYAMDNSRXTL-UHFFFAOYSA-N 0.000 description 1
- NOEUIMPIMKJGDC-UHFFFAOYSA-N N-[6-(4-fluorophenyl)-3-nitropyridin-2-yl]-6-piperazin-1-ylpyridine-3-carboxamide Chemical compound C1N(CCNC1)C1=NC=C(C=C1)C(=O)NC1=C(C=CC(C2=CC=C(F)C=C2)=N1)N(=O)=O NOEUIMPIMKJGDC-UHFFFAOYSA-N 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010029148 Nephrolithiasis Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 201000004317 Pitt-Hopkins syndrome Diseases 0.000 description 1
- 102100039388 Polyamine deacetylase HDAC10 Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 101150099493 STAT3 gene Proteins 0.000 description 1
- 108050002485 Sirtuin Proteins 0.000 description 1
- 102000011990 Sirtuin Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 description 1
- 208000011641 Spinocerebellar disease Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- RTKIYFITIVXBLE-UHFFFAOYSA-N Trichostatin A Natural products ONC(=O)C=CC(C)=CC(C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000003975 aryl alkyl amines Chemical class 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 description 1
- 229960003094 belinostat Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000001054 cardiac fibroblast Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000009025 developmental regulation Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 description 1
- 229960004515 diclofenac potassium Drugs 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000006718 epigenetic regulation Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- MSYBLBLAMDYKKZ-UHFFFAOYSA-N hydron;pyridine-3-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CN=C1 MSYBLBLAMDYKKZ-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940049920 malate Drugs 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000006993 memory improvement Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- DXHZSBAEWGPUKI-UHFFFAOYSA-N methyl 6-phenylpyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1C1=CC=CC=C1 DXHZSBAEWGPUKI-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- VOPDXHFYDJAYNS-UHFFFAOYSA-N n-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NCCCCCC(=O)NC1=CC=CC=C1N VOPDXHFYDJAYNS-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 101150054448 pdl-1 gene Proteins 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000024660 positive regulation of histone acetylation Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000001686 pro-survival effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical class OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 229960003452 romidepsin Drugs 0.000 description 1
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 description 1
- 108010091666 romidepsin Proteins 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- ATFXVNUWQOXRRU-UHFFFAOYSA-N taminadenant Chemical compound BrC=1C(N)=NC(N2N=CC=C2)=NC=1N1C=CC=N1 ATFXVNUWQOXRRU-UHFFFAOYSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- YFJSGGAEKPOTDP-UHFFFAOYSA-N tert-butyl N-[1-[5-[[6-(4-fluorophenyl)-3-nitropyridin-2-yl]carbamoyl]pyridin-2-yl]piperidin-4-yl]carbamate Chemical compound FC1=CC=C(C=C1)C1=CC=C(C(=N1)NC(=O)C=1C=CC(=NC=1)N1CCC(CC1)NC(OC(C)(C)C)=O)[N+](=O)[O-] YFJSGGAEKPOTDP-UHFFFAOYSA-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
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229960002044 tolmetin sodium Drugs 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
- 230000000699 topical effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17382447 | 2017-07-10 | ||
| PCT/ES2018/070491 WO2019012172A1 (es) | 2017-07-10 | 2018-07-09 | Nuevos derivados heteroaryl amida como inhibidores selectivos de histona deacetilasa 1 y 2 (hdac1/2) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2911040T3 true ES2911040T3 (es) | 2022-05-17 |
Family
ID=59315557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18789777T Active ES2911040T3 (es) | 2017-07-10 | 2018-07-09 | Nuevos derivados de heteroaril amida como inhibidores selectivos de histona deacetilasa 1 y 2 (HDAC1/2) |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US11241428B2 (enExample) |
| EP (1) | EP3653620B9 (enExample) |
| JP (1) | JP7026787B2 (enExample) |
| KR (1) | KR102574135B1 (enExample) |
| CN (1) | CN111051300B (enExample) |
| AU (1) | AU2018300123B2 (enExample) |
| CA (1) | CA3069273A1 (enExample) |
| CY (1) | CY1125343T1 (enExample) |
| DK (1) | DK3653620T3 (enExample) |
| EA (1) | EA039144B1 (enExample) |
| ES (1) | ES2911040T3 (enExample) |
| HR (1) | HRP20220472T1 (enExample) |
| HU (1) | HUE058353T2 (enExample) |
| LT (1) | LT3653620T (enExample) |
| MX (1) | MX393982B (enExample) |
| PL (1) | PL3653620T3 (enExample) |
| PT (1) | PT3653620T (enExample) |
| RS (1) | RS63156B1 (enExample) |
| SI (1) | SI3653620T1 (enExample) |
| SM (1) | SMT202200165T1 (enExample) |
| WO (1) | WO2019012172A1 (enExample) |
| ZA (1) | ZA202000727B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230119479A1 (en) * | 2019-12-10 | 2023-04-20 | Shionogi & Co., Ltd. | A histone deacetylase inhibitor having a nitrogen-containing aromatic heterocyclyl group |
| CN114380751B (zh) * | 2020-03-30 | 2025-03-07 | 上海辉启生物医药科技有限公司 | 二氢化茚胺类衍生物、其制备方法和用途 |
| MX2024006684A (es) | 2021-12-03 | 2024-08-26 | Tango Therapeutics Inc | Inhibidores de hdac novedosos y uso terapéutico de estos. |
| CN114524799B (zh) * | 2022-03-11 | 2023-05-26 | 沈阳药科大学 | 一种hdac抑制剂及其制备方法和用途 |
| EP4306106A1 (en) * | 2022-07-14 | 2024-01-17 | Universidade de Aveiro | Nitro-containing compounds, compositions and uses thereof |
| CN115463215A (zh) * | 2022-07-26 | 2022-12-13 | 苏州大学 | Hdac9及其抑制剂的新用途 |
| AU2023320136A1 (en) | 2022-08-05 | 2025-02-13 | Tango Therapeutics, Inc. | An hdac inhibitor for treating cancer with a modified stk11 activity or expression |
| CN115304513A (zh) * | 2022-08-25 | 2022-11-08 | 湖北科技学院 | 具有抗炎活性的查尔酮类衍生物及其合成方法和应用 |
| CN115368277B (zh) * | 2022-09-15 | 2024-03-29 | 华侨大学 | 一种含异羟肟酸结构的联苯类化合物及其应用 |
| CN116199636A (zh) * | 2023-02-21 | 2023-06-02 | 杭州医学院 | 靶向肿瘤免疫激酶的2,4-二取代嘧啶衍生物、制备方法及其应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2626898A1 (en) | 2005-11-03 | 2007-05-18 | Christopher Hamblett | Substituted nicotinamide compounds |
| EP2013196B1 (en) | 2006-04-26 | 2015-09-16 | Merck Sharp & Dohme Corp. | Disubstituted aniline compounds |
| WO2009005638A2 (en) | 2007-06-27 | 2009-01-08 | Merck & Co., Inc. | Pyridyl and pyrimidinyl derivatives as histone deacetylase inhibitors |
| EP2440519A1 (en) | 2009-06-08 | 2012-04-18 | Gilead Sciences, Inc. | Alkanoylamino benzamide aniline hdac inihibitor compounds |
| US20160137630A1 (en) * | 2014-10-08 | 2016-05-19 | Acetylon Pharmaceuticals, Inc. | Induction of gata2 by hdac1 and hdac2 inhibitors |
| KR20180022840A (ko) * | 2015-07-02 | 2018-03-06 | 바이오마린 파머수티컬 인크. | 히스톤 데아세틸라제 저해제 |
| US9603950B1 (en) * | 2015-10-25 | 2017-03-28 | Institute Of Nuclear Energy Research | Compounds of imaging agent with HDAC inhibitor for treatment of Alzheimer syndrome and method of synthesis thereof |
-
2018
- 2018-07-09 MX MX2020000349A patent/MX393982B/es unknown
- 2018-07-09 KR KR1020207003894A patent/KR102574135B1/ko active Active
- 2018-07-09 EA EA202090259A patent/EA039144B1/ru unknown
- 2018-07-09 SI SI201830644T patent/SI3653620T1/sl unknown
- 2018-07-09 HU HUE18789777A patent/HUE058353T2/hu unknown
- 2018-07-09 US US16/629,457 patent/US11241428B2/en active Active
- 2018-07-09 SM SM20220165T patent/SMT202200165T1/it unknown
- 2018-07-09 ES ES18789777T patent/ES2911040T3/es active Active
- 2018-07-09 JP JP2020523052A patent/JP7026787B2/ja active Active
- 2018-07-09 DK DK18789777.2T patent/DK3653620T3/da active
- 2018-07-09 RS RS20220320A patent/RS63156B1/sr unknown
- 2018-07-09 PT PT187897772T patent/PT3653620T/pt unknown
- 2018-07-09 CA CA3069273A patent/CA3069273A1/en active Pending
- 2018-07-09 WO PCT/ES2018/070491 patent/WO2019012172A1/es not_active Ceased
- 2018-07-09 LT LTEPPCT/ES2018/070491T patent/LT3653620T/lt unknown
- 2018-07-09 HR HRP20220472TT patent/HRP20220472T1/hr unknown
- 2018-07-09 AU AU2018300123A patent/AU2018300123B2/en active Active
- 2018-07-09 PL PL18789777T patent/PL3653620T3/pl unknown
- 2018-07-09 EP EP18789777.2A patent/EP3653620B9/en active Active
- 2018-07-09 CN CN201880056722.5A patent/CN111051300B/zh active Active
-
2020
- 2020-02-04 ZA ZA2020/00727A patent/ZA202000727B/en unknown
-
2022
- 2022-04-15 CY CY20221100286T patent/CY1125343T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL3653620T3 (pl) | 2022-06-20 |
| EP3653620B9 (en) | 2022-03-23 |
| MX393982B (es) | 2025-03-24 |
| RS63156B1 (sr) | 2022-05-31 |
| US11241428B2 (en) | 2022-02-08 |
| BR112020000564A2 (pt) | 2020-07-21 |
| KR20200038473A (ko) | 2020-04-13 |
| AU2018300123A1 (en) | 2020-02-13 |
| KR102574135B1 (ko) | 2023-09-01 |
| CN111051300B (zh) | 2022-12-23 |
| CN111051300A (zh) | 2020-04-21 |
| MX2020000349A (es) | 2020-08-17 |
| EP3653620A1 (en) | 2020-05-20 |
| EP3653620B1 (en) | 2022-02-02 |
| JP2020527173A (ja) | 2020-09-03 |
| ZA202000727B (en) | 2022-07-27 |
| SMT202200165T1 (it) | 2022-05-12 |
| JP7026787B2 (ja) | 2022-02-28 |
| HUE058353T2 (hu) | 2022-07-28 |
| WO2019012172A1 (es) | 2019-01-17 |
| LT3653620T (lt) | 2022-05-10 |
| CY1125343T1 (el) | 2024-12-13 |
| PT3653620T (pt) | 2022-04-22 |
| AU2018300123B2 (en) | 2022-03-17 |
| US20200138808A1 (en) | 2020-05-07 |
| DK3653620T3 (da) | 2022-03-28 |
| HRP20220472T1 (hr) | 2022-05-27 |
| CA3069273A1 (en) | 2019-01-17 |
| EA202090259A1 (ru) | 2020-05-25 |
| EA039144B1 (ru) | 2021-12-09 |
| SI3653620T1 (sl) | 2022-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2911040T3 (es) | Nuevos derivados de heteroaril amida como inhibidores selectivos de histona deacetilasa 1 y 2 (HDAC1/2) | |
| ES3036123T3 (en) | Heterocyclic rip1 kinase inhibitors | |
| CN108314677B (zh) | 一种ezh2抑制剂及其用途 | |
| ES2660215T3 (es) | Potenciador de efecto antitumoral que comprende un compuesto de imidazooxazina | |
| US9890168B2 (en) | 2,4-disubstituted 7H-pyrrolo[2,3-d]pyrimidine derivative, preparation method and medicinal use thereof | |
| KR20200028966A (ko) | Efgr 티로신 키나제의 임상적으로 중요한 돌연변이체의 선택적 억제제 | |
| TW201105326A (en) | Diamino heterocyclic carboxamide compound | |
| JP2020525513A (ja) | 癌および他の疾患を治療するためのａｔｆ４阻害剤としてのｎ−（３−（２−（４−クロロフェノキシ）アセトアミドビシクロ［１．１．１］ペンタン−１−イル）−２−シクロブタン−１−カルボキサミド誘導体および関連化合物 | |
| KR20170101908A (ko) | 피리미딘 또는 피리딘계 화합물, 이의 제조방법 및 약학적 용도 | |
| WO2016082713A1 (zh) | 2-氨基嘧啶类化合物及其药物组合物和应用 | |
| AU2017226005A1 (en) | Inhibitors of WDR5 protein-protein binding | |
| TW201625620A (zh) | 作為蛋白去乙醯酶抑制劑及雙蛋白去乙醯酶蛋白激酶抑制劑之雜環氧肟酸及其使用方法 | |
| AU2016382372B2 (en) | Sulfonamide derivative and preparation method and use thereof | |
| AU2019218187B2 (en) | Dioxinoquinoline compounds, preparation method and uses thereof | |
| CN105722840B (zh) | 作为PI3K、mTOR抑制剂的稠合喹啉化合物 | |
| WO2018153293A1 (zh) | 二噁烷并喹唑啉与二噁烷并喹啉类化合物及其制备方法与应用 | |
| CN107531683A (zh) | Usp7抑制剂化合物及使用方法 | |
| ES2389678T3 (es) | Un inhibidor de la quinasa C-Kit para su uso en el tratamiento de tumores del estroma gastrointestinal o mastocitosis | |
| JP2019514951A (ja) | 増殖性疾患の治療に使用される置換２，４−ジアミノ−キノリン誘導体 | |
| CN103648500B (zh) | 双功能酶制钳型分子的方法和用途 | |
| ES2782113T3 (es) | Compuestos de quinolina fusionados como inhibidores de PI3K/mTor | |
| WO2016140501A1 (en) | Pyridine n-oxide for enhancer of zeste homolog 2 inhibitors | |
| CA3178647A1 (en) | Substituted tricyclic amides, analogues thereof, and methods using same | |
| TW201033216A (en) | Pyrrolidine compounds | |
| BR112020000564B1 (pt) | Composto de heteroarilamida como inibidor seletivo das histonas desacetilases 1 e/ou 2 (hdac1-2), composição farmacêutica, uso e combinação do mesmo |