JP2008515985A - ナンセンス抑制の化合物とその使用方法 - Google Patents
ナンセンス抑制の化合物とその使用方法 Download PDFInfo
- Publication number
- JP2008515985A JP2008515985A JP2007536837A JP2007536837A JP2008515985A JP 2008515985 A JP2008515985 A JP 2008515985A JP 2007536837 A JP2007536837 A JP 2007536837A JP 2007536837 A JP2007536837 A JP 2007536837A JP 2008515985 A JP2008515985 A JP 2008515985A
- Authority
- JP
- Japan
- Prior art keywords
- group
- optionally substituted
- cancer
- alkyl
- compound
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 367
- 238000000034 method Methods 0.000 title claims abstract description 171
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 9
- 108020004485 Nonsense Codon Proteins 0.000 claims abstract description 96
- 230000037434 nonsense mutation Effects 0.000 claims abstract description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 63
- 201000010099 disease Diseases 0.000 claims abstract description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 107
- 150000002367 halogens Chemical group 0.000 claims description 101
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 206010028980 Neoplasm Diseases 0.000 claims description 87
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 81
- 239000002904 solvent Substances 0.000 claims description 75
- 210000004027 cell Anatomy 0.000 claims description 66
- 201000011510 cancer Diseases 0.000 claims description 62
- 108090000623 proteins and genes Proteins 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 59
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 59
- 238000002360 preparation method Methods 0.000 claims description 57
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 102000004169 proteins and genes Human genes 0.000 claims description 40
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 36
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 32
- 230000035772 mutation Effects 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 201000006938 muscular dystrophy Diseases 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000003277 amino group Chemical group 0.000 claims description 22
- 125000004104 aryloxy group Chemical group 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 20
- 239000012453 solvate Substances 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 16
- 206010039491 Sarcoma Diseases 0.000 claims description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 13
- 208000031220 Hemophilia Diseases 0.000 claims description 13
- 208000009292 Hemophilia A Diseases 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000001990 intravenous administration Methods 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 208000009956 adenocarcinoma Diseases 0.000 claims description 10
- 208000015114 central nervous system disease Diseases 0.000 claims description 10
- 230000003511 endothelial effect Effects 0.000 claims description 10
- 108700025694 p53 Genes Proteins 0.000 claims description 10
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 208000032839 leukemia Diseases 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- 208000027932 Collagen disease Diseases 0.000 claims description 8
- 208000014951 hematologic disease Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 7
- 208000034578 Multiple myelomas Diseases 0.000 claims description 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- 208000008383 Wilms tumor Diseases 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 201000005202 lung cancer Diseases 0.000 claims description 7
- 201000008026 nephroblastoma Diseases 0.000 claims description 7
- 201000002528 pancreatic cancer Diseases 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 6
- 206010069754 Acquired gene mutation Diseases 0.000 claims description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 208000019838 Blood disease Diseases 0.000 claims description 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 6
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 6
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 6
- 201000000582 Retinoblastoma Diseases 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 6
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical group C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 230000037439 somatic mutation Effects 0.000 claims description 6
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 6
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 5
- 201000003076 Angiosarcoma Diseases 0.000 claims description 5
- 206010003571 Astrocytoma Diseases 0.000 claims description 5
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 5
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 5
- 201000009047 Chordoma Diseases 0.000 claims description 5
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 5
- 208000009798 Craniopharyngioma Diseases 0.000 claims description 5
- 206010014967 Ependymoma Diseases 0.000 claims description 5
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 5
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 5
- 208000032612 Glial tumor Diseases 0.000 claims description 5
- 206010018338 Glioma Diseases 0.000 claims description 5
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 5
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 5
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 5
- 208000000172 Medulloblastoma Diseases 0.000 claims description 5
- 206010027406 Mesothelioma Diseases 0.000 claims description 5
- 208000014060 Niemann-Pick disease Diseases 0.000 claims description 5
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 5
- 201000010208 Seminoma Diseases 0.000 claims description 5
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 5
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 5
- 208000014070 Vestibular schwannoma Diseases 0.000 claims description 5
- 208000004064 acoustic neuroma Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 claims description 5
- 201000010881 cervical cancer Diseases 0.000 claims description 5
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 208000002445 cystadenocarcinoma Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 206010024627 liposarcoma Diseases 0.000 claims description 5
- 201000007270 liver cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 208000012804 lymphangiosarcoma Diseases 0.000 claims description 5
- 230000001926 lymphatic effect Effects 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 206010027191 meningioma Diseases 0.000 claims description 5
- 208000001611 myxosarcoma Diseases 0.000 claims description 5
- 201000008968 osteosarcoma Diseases 0.000 claims description 5
- 210000000496 pancreas Anatomy 0.000 claims description 5
- 208000004019 papillary adenocarcinoma Diseases 0.000 claims description 5
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 5
- 208000018964 sebaceous gland cancer Diseases 0.000 claims description 5
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 5
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 5
- 201000003120 testicular cancer Diseases 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 208000005440 Basal Cell Neoplasms Diseases 0.000 claims description 4
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010013883 Dwarfism Diseases 0.000 claims description 4
- 201000009051 Embryonal Carcinoma Diseases 0.000 claims description 4
- 206010020850 Hyperthyroidism Diseases 0.000 claims description 4
- 208000019693 Lung disease Diseases 0.000 claims description 4
- 208000001826 Marfan syndrome Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000022292 Tay-Sachs disease Diseases 0.000 claims description 4
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 4
- 230000032683 aging Effects 0.000 claims description 4
- 206010002022 amyloidosis Diseases 0.000 claims description 4
- 208000003362 bronchogenic carcinoma Diseases 0.000 claims description 4
- 230000007882 cirrhosis Effects 0.000 claims description 4
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 210000003238 esophagus Anatomy 0.000 claims description 4
- 210000001508 eye Anatomy 0.000 claims description 4
- 201000002222 hemangioblastoma Diseases 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 208000025189 neoplasm of testis Diseases 0.000 claims description 4
- 210000003757 neuroblast Anatomy 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 201000008759 sweat gland cancer Diseases 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 3
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 claims description 3
- 206010003591 Ataxia Diseases 0.000 claims description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
- 208000000913 Kidney Calculi Diseases 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 claims description 3
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 claims description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 3
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 claims description 3
- 206010029148 Nephrolithiasis Diseases 0.000 claims description 3
- 206010031243 Osteogenesis imperfecta Diseases 0.000 claims description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 3
- 208000027276 Von Willebrand disease Diseases 0.000 claims description 3
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 claims description 3
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 claims description 3
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 claims description 3
- 208000036676 acute undifferentiated leukemia Diseases 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 208000005980 beta thalassemia Diseases 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 201000005577 familial hyperlipidemia Diseases 0.000 claims description 3
- 208000024908 graft versus host disease Diseases 0.000 claims description 3
- 210000003128 head Anatomy 0.000 claims description 3
- 210000002216 heart Anatomy 0.000 claims description 3
- 210000000936 intestine Anatomy 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 210000000214 mouth Anatomy 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 210000003739 neck Anatomy 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 210000003800 pharynx Anatomy 0.000 claims description 3
- 210000004560 pineal gland Anatomy 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 210000000664 rectum Anatomy 0.000 claims description 3
- 210000001599 sigmoid colon Anatomy 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 claims description 3
- 208000031206 Familial polycythaemia Diseases 0.000 claims description 2
- 206010061598 Immunodeficiency Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 208000037550 Primary familial polycythemia Diseases 0.000 claims description 2
- 208000037832 acute lymphoblastic B-cell leukemia Diseases 0.000 claims description 2
- 208000037833 acute lymphoblastic T-cell leukemia Diseases 0.000 claims description 2
- 201000005188 adrenal gland cancer Diseases 0.000 claims description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 claims description 2
- 230000005907 cancer growth Effects 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000002768 hair cell Anatomy 0.000 claims description 2
- 201000010235 heart cancer Diseases 0.000 claims description 2
- 208000024348 heart neoplasm Diseases 0.000 claims description 2
- 230000007813 immunodeficiency Effects 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 201000006870 primary polycythemia Diseases 0.000 claims description 2
- 230000000304 vasodilatating effect Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 118
- 108020004999 messenger RNA Proteins 0.000 abstract description 51
- 238000013519 translation Methods 0.000 abstract description 50
- 230000002028 premature Effects 0.000 abstract description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 131
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 113
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 88
- 239000000243 solution Substances 0.000 description 88
- -1 alkyl radical Chemical class 0.000 description 79
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- 239000007787 solid Substances 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- 238000006243 chemical reaction Methods 0.000 description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 230000014616 translation Effects 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 49
- 239000011347 resin Substances 0.000 description 48
- 229920005989 resin Polymers 0.000 description 48
- 239000011734 sodium Substances 0.000 description 47
- 238000005481 NMR spectroscopy Methods 0.000 description 43
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 42
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- 238000010992 reflux Methods 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 28
- 239000000047 product Substances 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 108060001084 Luciferase Proteins 0.000 description 27
- 108020005038 Terminator Codon Proteins 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 26
- 239000000725 suspension Substances 0.000 description 26
- 150000002431 hydrogen Chemical class 0.000 description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
- 238000010171 animal model Methods 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 238000003556 assay Methods 0.000 description 22
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 22
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- 230000001629 suppression Effects 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- 238000003818 flash chromatography Methods 0.000 description 19
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 239000000843 powder Substances 0.000 description 17
- 150000002148 esters Chemical class 0.000 description 16
- 239000012442 inert solvent Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 108020004705 Codon Proteins 0.000 description 15
- 239000005089 Luciferase Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- 239000000654 additive Substances 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 11
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 150000007523 nucleic acids Chemical class 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 108020004707 nucleic acids Proteins 0.000 description 10
- 102000039446 nucleic acids Human genes 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 239000005711 Benzoic acid Substances 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 230000003197 catalytic effect Effects 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 8
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 8
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
- 108020004566 Transfer RNA Proteins 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 208000015439 Lysosomal storage disease Diseases 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 229930192474 thiophene Natural products 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000007872 degassing Methods 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 230000001537 neural effect Effects 0.000 description 6
- 150000002916 oxazoles Chemical class 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 238000005192 partition Methods 0.000 description 6
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000003586 protic polar solvent Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 238000011830 transgenic mouse model Methods 0.000 description 6
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 229930024421 Adenine Natural products 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 5
- 229930182566 Gentamicin Natural products 0.000 description 5
- 108010039203 Tripeptidyl-Peptidase 1 Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 229960000643 adenine Drugs 0.000 description 5
- 150000001409 amidines Chemical class 0.000 description 5
- 229940126575 aminoglycoside Drugs 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940104302 cytosine Drugs 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 229960002518 gentamicin Drugs 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- RYFZYYUIAZYQLC-UHFFFAOYSA-N perchloromethyl mercaptan Chemical compound ClSC(Cl)(Cl)Cl RYFZYYUIAZYQLC-UHFFFAOYSA-N 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 150000003557 thiazoles Chemical class 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 150000005071 1,2,4-oxadiazoles Chemical class 0.000 description 4
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical class C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- HWAGRGIKLYWPKC-UHFFFAOYSA-N 3-[3-(4-chlorophenyl)-1,2-oxazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2ON=C(C=2)C=2C=CC(Cl)=CC=2)=C1 HWAGRGIKLYWPKC-UHFFFAOYSA-N 0.000 description 4
- 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 102100034197 Tripeptidyl-peptidase 1 Human genes 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 150000007929 acylimidazolides Chemical class 0.000 description 4
- 125000003275 alpha amino acid group Chemical group 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 238000010256 biochemical assay Methods 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 4
- 238000011813 knockout mouse model Methods 0.000 description 4
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 238000003468 luciferase reporter gene assay Methods 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- QOUUCORIWWWPLU-UHFFFAOYSA-N methyl 3-(2-bromoacetyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)CBr)=C1 QOUUCORIWWWPLU-UHFFFAOYSA-N 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- CKMXAIVXVKGGFM-UHFFFAOYSA-N p-cumic acid Chemical compound CC(C)C1=CC=C(C(O)=O)C=C1 CKMXAIVXVKGGFM-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 229940113082 thymine Drugs 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical group CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 4
- 229910052721 tungsten Inorganic materials 0.000 description 4
- REHVCPNQQBDOJJ-UHFFFAOYSA-N (3-ethoxycarbonylphenyl)boronic acid Chemical compound CCOC(=O)C1=CC=CC(B(O)O)=C1 REHVCPNQQBDOJJ-UHFFFAOYSA-N 0.000 description 3
- IAEUFBDMVKQCLU-UHFFFAOYSA-N (4-propan-2-ylphenyl)boronic acid Chemical compound CC(C)C1=CC=C(B(O)O)C=C1 IAEUFBDMVKQCLU-UHFFFAOYSA-N 0.000 description 3
- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 description 3
- BUXDZKJHNFMYJT-UHFFFAOYSA-N 2,3-diiodothiophene Chemical compound IC=1C=CSC=1I BUXDZKJHNFMYJT-UHFFFAOYSA-N 0.000 description 3
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 3
- ZSCDQVYYLJSTFU-UHFFFAOYSA-N 2-bromo-1-(4-propan-2-ylphenyl)ethanone Chemical compound CC(C)C1=CC=C(C(=O)CBr)C=C1 ZSCDQVYYLJSTFU-UHFFFAOYSA-N 0.000 description 3
- ODEXZMVMVLPNAC-UHFFFAOYSA-N 3-[2-(4-propan-2-ylphenyl)-1,3-thiazol-4-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(C=2C=C(C=CC=2)C(O)=O)=CS1 ODEXZMVMVLPNAC-UHFFFAOYSA-N 0.000 description 3
- XBABSHRXKNGEPL-UHFFFAOYSA-N 3-[2-(4-propan-2-ylphenyl)-1,3-thiazol-5-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC=C(C=2C=C(C=CC=2)C(O)=O)S1 XBABSHRXKNGEPL-UHFFFAOYSA-N 0.000 description 3
- IIFXXCNURBTBOX-UHFFFAOYSA-N 3-[3-(4-fluorophenyl)-3-oxopropanoyl]benzonitrile Chemical compound C1=CC(F)=CC=C1C(=O)CC(=O)C1=CC=CC(C#N)=C1 IIFXXCNURBTBOX-UHFFFAOYSA-N 0.000 description 3
- MENDHRQYFMVGJG-UHFFFAOYSA-N 3-[3-(4-propan-2-ylphenyl)-1,2,4-thiadiazol-5-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NSC(C=2C=C(C=CC=2)C(O)=O)=N1 MENDHRQYFMVGJG-UHFFFAOYSA-N 0.000 description 3
- ZMWOKONFALOMHQ-UHFFFAOYSA-N 3-[4-(4-methylphenyl)-1,3-thiazol-2-yl]benzoic acid Chemical compound C1=CC(C)=CC=C1C1=CSC(C=2C=C(C=CC=2)C(O)=O)=N1 ZMWOKONFALOMHQ-UHFFFAOYSA-N 0.000 description 3
- WINFAGYYMOORGC-UHFFFAOYSA-N 3-[4-(4-propan-2-ylphenyl)-1,3-thiazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CSC(C=2C=C(C=CC=2)C(O)=O)=N1 WINFAGYYMOORGC-UHFFFAOYSA-N 0.000 description 3
- BCNBWWKWQWXKSV-UHFFFAOYSA-N 3-[4-(4-propan-2-ylphenyl)thiophen-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CSC(C=2C=C(C=CC=2)C(O)=O)=C1 BCNBWWKWQWXKSV-UHFFFAOYSA-N 0.000 description 3
- PVHDLTOUJMLJAL-UHFFFAOYSA-N 3-[4-(4-pyrrolidin-1-ylphenyl)-1,3-oxazol-2-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2OC=C(N=2)C=2C=CC(=CC=2)N2CCCC2)=C1 PVHDLTOUJMLJAL-UHFFFAOYSA-N 0.000 description 3
- VLYGWCBCTBQYBS-UHFFFAOYSA-N 3-[5-(4-chlorophenyl)-1,2-oxazol-3-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C2=NOC(=C2)C=2C=CC(Cl)=CC=2)=C1 VLYGWCBCTBQYBS-UHFFFAOYSA-N 0.000 description 3
- KLSDXVUPZQEBDQ-UHFFFAOYSA-N 3-[5-(4-fluorophenyl)-1h-pyrazol-3-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C2=NNC(=C2)C=2C=CC(F)=CC=2)=C1 KLSDXVUPZQEBDQ-UHFFFAOYSA-N 0.000 description 3
- KTUWAIJEMXVGNR-UHFFFAOYSA-N 3-[5-(4-fluorophenyl)-1h-pyrazol-3-yl]benzonitrile Chemical compound C1=CC(F)=CC=C1C1=CC(C=2C=C(C=CC=2)C#N)=NN1 KTUWAIJEMXVGNR-UHFFFAOYSA-N 0.000 description 3
- QBKNLYXRAPNXKO-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1,2,4-thiadiazol-3-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(C=2C=C(C=CC=2)C(O)=O)=NS1 QBKNLYXRAPNXKO-UHFFFAOYSA-N 0.000 description 3
- KCRWPKSLJBRLRW-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1,3,4-oxadiazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NN=C(C=2C=C(C=CC=2)C(O)=O)O1 KCRWPKSLJBRLRW-UHFFFAOYSA-N 0.000 description 3
- IFNYPXQFUKSRKB-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)thiophen-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CC=C(C=2C=C(C=CC=2)C(O)=O)S1 IFNYPXQFUKSRKB-UHFFFAOYSA-N 0.000 description 3
- LSVJJDJSDGYBES-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)thiophen-3-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CC(C=2C=C(C=CC=2)C(O)=O)=CS1 LSVJJDJSDGYBES-UHFFFAOYSA-N 0.000 description 3
- KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 description 3
- JFYDEFSWRWLDGE-UHFFFAOYSA-N 4-propan-2-ylbenzamide Chemical compound CC(C)C1=CC=C(C(N)=O)C=C1 JFYDEFSWRWLDGE-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 3
- 102100032752 C-reactive protein Human genes 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- 150000000475 acetylene derivatives Chemical group 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- 230000001668 ameliorated effect Effects 0.000 description 3
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RDYMFSUJUZBWLH-UHFFFAOYSA-N endosulfan Chemical compound C12COS(=O)OCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl RDYMFSUJUZBWLH-UHFFFAOYSA-N 0.000 description 3
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 3
- OILHDBLLQZLFFI-UHFFFAOYSA-N ethoxy-ethylsulfanyl-hydroxy-sulfanylidene-$l^{5}-phosphane Chemical compound CCOP(O)(=S)SCC OILHDBLLQZLFFI-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 210000003292 kidney cell Anatomy 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 150000004667 medium chain fatty acids Chemical class 0.000 description 3
- KZGRSYGDDBGHOO-UHFFFAOYSA-N methyl 3-(hydroxyiminomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(C=NO)=C1 KZGRSYGDDBGHOO-UHFFFAOYSA-N 0.000 description 3
- ILTCFMJZQGMOEA-UHFFFAOYSA-N methyl 3-[2-[(4-propan-2-ylbenzoyl)amino]acetyl]benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)CNC(=O)C=2C=CC(=CC=2)C(C)C)=C1 ILTCFMJZQGMOEA-UHFFFAOYSA-N 0.000 description 3
- XPBHWSMZTSSEJE-UHFFFAOYSA-N methyl 3-cyanobenzoate Chemical compound COC(=O)C1=CC=CC(C#N)=C1 XPBHWSMZTSSEJE-UHFFFAOYSA-N 0.000 description 3
- VHEWHAWQKJTQCA-UHFFFAOYSA-N methyl 4-(4,5-dihydro-1,3-oxazol-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NCCO1 VHEWHAWQKJTQCA-UHFFFAOYSA-N 0.000 description 3
- IEVQGSFQDDGGHI-UHFFFAOYSA-N methyl 4-[5-[3-[(4-propan-2-ylphenyl)carbamoylamino]phenyl]-1,3,4-oxadiazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NN=C(C=2C=C(NC(=O)NC=3C=CC(=CC=3)C(C)C)C=CC=2)O1 IEVQGSFQDDGGHI-UHFFFAOYSA-N 0.000 description 3
- CVXXHXPNTZBZEL-UHFFFAOYSA-N methyl 4-carbonochloridoylbenzoate Chemical compound COC(=O)C1=CC=C(C(Cl)=O)C=C1 CVXXHXPNTZBZEL-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 238000001243 protein synthesis Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 108091007054 readthrough proteins Proteins 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 150000003536 tetrazoles Chemical class 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 150000003577 thiophenes Chemical class 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- PDLCCNYKIIUWHA-UHFFFAOYSA-N 1-(4-propan-2-ylphenyl)ethanone Chemical compound CC(C)C1=CC=C(C(C)=O)C=C1 PDLCCNYKIIUWHA-UHFFFAOYSA-N 0.000 description 2
- UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- WAQFYSJKIRRXLP-UHFFFAOYSA-N 2,4-dibromothiophene Chemical compound BrC1=CSC(Br)=C1 WAQFYSJKIRRXLP-UHFFFAOYSA-N 0.000 description 2
- KBVDUUXRXJTAJC-UHFFFAOYSA-N 2,5-dibromothiophene Chemical compound BrC1=CC=C(Br)S1 KBVDUUXRXJTAJC-UHFFFAOYSA-N 0.000 description 2
- RJRLLFDNNYQIPY-UHFFFAOYSA-N 2-amino-1-(4-propan-2-ylphenyl)ethanone;hydrochloride Chemical compound Cl.CC(C)C1=CC=C(C(=O)CN)C=C1 RJRLLFDNNYQIPY-UHFFFAOYSA-N 0.000 description 2
- YCHPNSOKVRTPES-UHFFFAOYSA-N 2-bromo-1,3-oxazole Chemical compound BrC1=NC=CO1 YCHPNSOKVRTPES-UHFFFAOYSA-N 0.000 description 2
- AEBBXVHGVADBHA-UHFFFAOYSA-M 2-chloro-1,3-dimethyl-4,5-dihydroimidazol-1-ium;chloride Chemical compound [Cl-].CN1CC[N+](C)=C1Cl AEBBXVHGVADBHA-UHFFFAOYSA-M 0.000 description 2
- DTNSDCJFTHMDAK-UHFFFAOYSA-N 2-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C#N DTNSDCJFTHMDAK-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- GIYMUNNMKVHGJK-UHFFFAOYSA-N 3-[2-(4-propan-2-ylphenyl)-1,3-oxazol-5-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC=C(C=2C=C(C=CC=2)C(O)=O)O1 GIYMUNNMKVHGJK-UHFFFAOYSA-N 0.000 description 2
- GSPFWEQYHDJIMJ-UHFFFAOYSA-N 3-[2-(4-propan-2-ylphenyl)-1h-imidazol-5-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC=C(C=2C=C(C=CC=2)C(O)=O)N1 GSPFWEQYHDJIMJ-UHFFFAOYSA-N 0.000 description 2
- CJIHRCOLIUXECG-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1,3-oxazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CN=C(C=2C=C(C=CC=2)C(O)=O)O1 CJIHRCOLIUXECG-UHFFFAOYSA-N 0.000 description 2
- PWEDEXDVUCWHMG-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1h-imidazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CN=C(C=2C=C(C=CC=2)C(O)=O)N1 PWEDEXDVUCWHMG-UHFFFAOYSA-N 0.000 description 2
- GRIPBQJVPFRLHA-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1h-pyrazol-3-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NNC(C=2C=C(C=CC=2)C(O)=O)=C1 GRIPBQJVPFRLHA-UHFFFAOYSA-N 0.000 description 2
- SOWFHEBUCNJJMK-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)furan-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CC=C(C=2C=C(C=CC=2)C(O)=O)O1 SOWFHEBUCNJJMK-UHFFFAOYSA-N 0.000 description 2
- YNHKKSMYDIEQKY-UHFFFAOYSA-N 3-carbamothioylbenzoic acid Chemical compound NC(=S)C1=CC=CC(C(O)=O)=C1 YNHKKSMYDIEQKY-UHFFFAOYSA-N 0.000 description 2
- DXVWRNXWHABIBB-UHFFFAOYSA-N 4-[5-[3-[(4-methylphenyl)sulfonylamino]phenyl]-1,3,4-oxadiazol-2-yl]benzoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC(C=2OC(=NN=2)C=2C=CC(=CC=2)C(O)=O)=C1 DXVWRNXWHABIBB-UHFFFAOYSA-N 0.000 description 2
- VQSUMYHLBMUMRL-UHFFFAOYSA-N 4-bromo-2-(4-propan-2-ylphenyl)thiophene Chemical compound C1=CC(C(C)C)=CC=C1C1=CC(Br)=CS1 VQSUMYHLBMUMRL-UHFFFAOYSA-N 0.000 description 2
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical group OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- SDNLXXUGUAWDAT-UHFFFAOYSA-N 4-propan-2-ylbenzenecarbothioamide Chemical compound CC(C)C1=CC=C(C(N)=S)C=C1 SDNLXXUGUAWDAT-UHFFFAOYSA-N 0.000 description 2
- YFDJCWXBKWRDPW-UHFFFAOYSA-N 4-propan-2-ylbenzonitrile Chemical compound CC(C)C1=CC=C(C#N)C=C1 YFDJCWXBKWRDPW-UHFFFAOYSA-N 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 102000052866 Amino Acyl-tRNA Synthetases Human genes 0.000 description 2
- 108700028939 Amino Acyl-tRNA Synthetases Proteins 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 2
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
- 108010062745 Chloride Channels Proteins 0.000 description 2
- 102000011045 Chloride Channels Human genes 0.000 description 2
- OHEMBWZZEKCBAS-UUOKFMHZSA-N Clitocine Chemical compound NC1=NC=NC(N[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1[N+]([O-])=O OHEMBWZZEKCBAS-UUOKFMHZSA-N 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 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
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 2
- 102000001039 Dystrophin Human genes 0.000 description 2
- 108010069091 Dystrophin Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 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 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 150000008062 acetophenones Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical class NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 238000013216 cat model Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 108091092356 cellular DNA Proteins 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229960002626 clarithromycin Drugs 0.000 description 2
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 2
- 239000012084 conversion product Substances 0.000 description 2
- 239000012045 crude solution Substances 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- VNGOYPQMJFJDLV-UHFFFAOYSA-N dimethyl benzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC=CC(C(=O)OC)=C1 VNGOYPQMJFJDLV-UHFFFAOYSA-N 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- XZYACMLXMFJXCD-UHFFFAOYSA-N ethyl 3-(4-bromothiophen-2-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC=C(Br)C=2)=C1 XZYACMLXMFJXCD-UHFFFAOYSA-N 0.000 description 2
- MJDFNXKRSXLJLW-UHFFFAOYSA-N ethyl 3-(5-bromothiophen-2-yl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC(Br)=CC=2)=C1 MJDFNXKRSXLJLW-UHFFFAOYSA-N 0.000 description 2
- BNUGAROUXYLJDO-UHFFFAOYSA-N ethyl 3-[3-(4-chlorophenyl)-1,2-oxazol-5-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2ON=C(C=2)C=2C=CC(Cl)=CC=2)=C1 BNUGAROUXYLJDO-UHFFFAOYSA-N 0.000 description 2
- NZJDNWAGDWPKGA-UHFFFAOYSA-N ethyl 3-[4-(4-propan-2-ylphenyl)thiophen-2-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC=C(C=2)C=2C=CC(=CC=2)C(C)C)=C1 NZJDNWAGDWPKGA-UHFFFAOYSA-N 0.000 description 2
- SSWKCDMUVMHCQJ-UHFFFAOYSA-N ethyl 3-[5-(4-propan-2-ylphenyl)-1,3-oxazol-2-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2OC(=CN=2)C=2C=CC(=CC=2)C(C)C)=C1 SSWKCDMUVMHCQJ-UHFFFAOYSA-N 0.000 description 2
- QFHWQTRLKBFLCG-UHFFFAOYSA-N ethyl 3-[5-(4-propan-2-ylphenyl)-1,3-thiazol-2-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC(=CN=2)C=2C=CC(=CC=2)C(C)C)=C1 QFHWQTRLKBFLCG-UHFFFAOYSA-N 0.000 description 2
- KFOAOTZWTXGFAF-UHFFFAOYSA-N ethyl 3-[5-(4-propan-2-ylphenyl)thiophen-3-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2C=C(SC=2)C=2C=CC(=CC=2)C(C)C)=C1 KFOAOTZWTXGFAF-UHFFFAOYSA-N 0.000 description 2
- MHUROOJYWQMISW-UHFFFAOYSA-N ethyl 3-carbamothioylbenzoate Chemical compound CCOC(=O)C1=CC=CC(C(N)=S)=C1 MHUROOJYWQMISW-UHFFFAOYSA-N 0.000 description 2
- ZKXMKMLGUYSGNS-UHFFFAOYSA-N ethyl 3-cyanobenzoate Chemical compound CCOC(=O)C1=CC=CC(C#N)=C1 ZKXMKMLGUYSGNS-UHFFFAOYSA-N 0.000 description 2
- DIZFWJVCPSJKGW-UHFFFAOYSA-N ethyl 3-ethynylbenzoate Chemical compound CCOC(=O)C1=CC=CC(C#C)=C1 DIZFWJVCPSJKGW-UHFFFAOYSA-N 0.000 description 2
- POGCXCWRMMXDAQ-UHFFFAOYSA-N ethyl 3-iodobenzoate Chemical compound CCOC(=O)C1=CC=CC(I)=C1 POGCXCWRMMXDAQ-UHFFFAOYSA-N 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000008241 heterogeneous mixture Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 230000002989 hypothyroidism Effects 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- VYLKDIBTVNWVEL-UHFFFAOYSA-N methyl 3-(2-oxo-1,3,4-oxathiazol-5-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=O)SN=2)=C1 VYLKDIBTVNWVEL-UHFFFAOYSA-N 0.000 description 2
- LYMJSMDTUDSRBZ-UHFFFAOYSA-N methyl 3-[2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2N=C(OC=2)C=2C=CC(=CC=2)C(C)C)=C1 LYMJSMDTUDSRBZ-UHFFFAOYSA-N 0.000 description 2
- PQSXAAIUCYTPHB-UHFFFAOYSA-N methyl 3-[2-(4-propan-2-ylphenyl)-1,3-oxazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NC=2)C=2C=CC(=CC=2)C(C)C)=C1 PQSXAAIUCYTPHB-UHFFFAOYSA-N 0.000 description 2
- PUZIZPXDZCEPIS-UHFFFAOYSA-N methyl 3-[2-(4-propan-2-ylphenyl)-1,3-thiazol-4-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2N=C(SC=2)C=2C=CC(=CC=2)C(C)C)=C1 PUZIZPXDZCEPIS-UHFFFAOYSA-N 0.000 description 2
- LJKIVTONDZEBLB-UHFFFAOYSA-N methyl 3-[2-(4-propan-2-ylphenyl)-1,3-thiazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2SC(=NC=2)C=2C=CC(=CC=2)C(C)C)=C1 LJKIVTONDZEBLB-UHFFFAOYSA-N 0.000 description 2
- VRDVUDGWIYXWAD-UHFFFAOYSA-N methyl 3-[2-ethoxycarbonyl-4-oxo-4-(4-propan-2-ylphenyl)butanoyl]benzoate Chemical compound C=1C=CC(C(=O)OC)=CC=1C(=O)C(C(=O)OCC)CC(=O)C1=CC=C(C(C)C)C=C1 VRDVUDGWIYXWAD-UHFFFAOYSA-N 0.000 description 2
- ATFZJGICZJSPTA-UHFFFAOYSA-N methyl 3-[2-methoxycarbonyl-4-oxo-4-(4-propan-2-ylphenyl)butanoyl]benzoate Chemical compound C=1C=CC(C(=O)OC)=CC=1C(=O)C(C(=O)OC)CC(=O)C1=CC=C(C(C)C)C=C1 ATFZJGICZJSPTA-UHFFFAOYSA-N 0.000 description 2
- GRRRMBOMTSXOEU-UHFFFAOYSA-N methyl 3-[3-oxo-3-(4-propan-2-ylphenyl)propanoyl]benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)CC(=O)C=2C=CC(=CC=2)C(C)C)=C1 GRRRMBOMTSXOEU-UHFFFAOYSA-N 0.000 description 2
- UNVFAZCHMKSLAB-UHFFFAOYSA-N methyl 3-[5-(4-chlorophenyl)-1,2-oxazol-3-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C2=NOC(=C2)C=2C=CC(Cl)=CC=2)=C1 UNVFAZCHMKSLAB-UHFFFAOYSA-N 0.000 description 2
- BMXCFTYOZJMRKE-UHFFFAOYSA-N methyl 3-[5-(4-morpholin-4-ylphenyl)-1,3,4-oxadiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NN=2)C=2C=CC(=CC=2)N2CCOCC2)=C1 BMXCFTYOZJMRKE-UHFFFAOYSA-N 0.000 description 2
- HXHCZLKPMCKQBS-UHFFFAOYSA-N methyl 3-[5-(4-propan-2-ylphenyl)-1,3,4-oxadiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NN=2)C=2C=CC(=CC=2)C(C)C)=C1 HXHCZLKPMCKQBS-UHFFFAOYSA-N 0.000 description 2
- IPLPTIXVHXGKPE-UHFFFAOYSA-N methyl 3-[5-(4-propan-2-ylphenyl)-1h-imidazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2NC(=CN=2)C=2C=CC(=CC=2)C(C)C)=C1 IPLPTIXVHXGKPE-UHFFFAOYSA-N 0.000 description 2
- IIEAHQJVTAWZPR-UHFFFAOYSA-N methyl 3-[5-(4-propan-2-ylphenyl)furan-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=CC=2)C=2C=CC(=CC=2)C(C)C)=C1 IIEAHQJVTAWZPR-UHFFFAOYSA-N 0.000 description 2
- QQZICUFZEGEJRV-UHFFFAOYSA-N methyl 3-[5-[4-(3-methylphenyl)phenyl]-1,3,4-oxadiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NN=2)C=2C=CC(=CC=2)C=2C=C(C)C=CC=2)=C1 QQZICUFZEGEJRV-UHFFFAOYSA-N 0.000 description 2
- NCNUIUIDKJSGDM-UHFFFAOYSA-N methyl 3-acetylbenzoate Chemical compound COC(=O)C1=CC=CC(C(C)=O)=C1 NCNUIUIDKJSGDM-UHFFFAOYSA-N 0.000 description 2
- UTGGIQHJOAPIPD-UHFFFAOYSA-N methyl 3-carbonochloridoylbenzoate Chemical compound COC(=O)C1=CC=CC(C(Cl)=O)=C1 UTGGIQHJOAPIPD-UHFFFAOYSA-N 0.000 description 2
- AOUVQJKORHYKOT-UHFFFAOYSA-N methyl 4-(5-bromo-1,3-oxazol-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC=C(Br)O1 AOUVQJKORHYKOT-UHFFFAOYSA-N 0.000 description 2
- LHZSVEQZVNXZJI-UHFFFAOYSA-N methyl 4-[5-(2,4-difluorophenyl)-1,3-oxazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC=C(C=2C(=CC(F)=CC=2)F)O1 LHZSVEQZVNXZJI-UHFFFAOYSA-N 0.000 description 2
- YZXQEEWXDHYHDB-UHFFFAOYSA-N methyl 4-[5-(3-aminophenyl)-1,3,4-oxadiazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NN=C(C=2C=C(N)C=CC=2)O1 YZXQEEWXDHYHDB-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 229960002446 octanoic acid Drugs 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 210000004708 ribosome subunit Anatomy 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 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 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- QQLRSCZSKQTFGY-UHFFFAOYSA-N (2,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1F QQLRSCZSKQTFGY-UHFFFAOYSA-N 0.000 description 1
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- QKWBTCRVPQHOMT-UITAMQMPSA-N (nz)-n-[(4-chlorophenyl)methylidene]hydroxylamine Chemical compound O\N=C/C1=CC=C(Cl)C=C1 QKWBTCRVPQHOMT-UITAMQMPSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- 150000000178 1,2,4-triazoles Chemical class 0.000 description 1
- 150000004869 1,3,4-thiadiazoles Chemical class 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- AWCLKERIODTIBX-UHFFFAOYSA-N 1,3-oxazol-2-yl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1=NC=CO1 AWCLKERIODTIBX-UHFFFAOYSA-N 0.000 description 1
- LFZJRTMTKGYJRS-UHFFFAOYSA-N 1-chloro-4-ethynylbenzene Chemical compound ClC1=CC=C(C#C)C=C1 LFZJRTMTKGYJRS-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- PJVRNNRZWASOIT-UHFFFAOYSA-N 1-isocyanato-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(N=C=O)C=C1 PJVRNNRZWASOIT-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical compound C1NC=CO1 ZABMHLDQFJHDSC-UHFFFAOYSA-N 0.000 description 1
- KRAWAGMBRSAXDJ-UHFFFAOYSA-N 2-(1h-pyrazol-5-yl)benzonitrile Chemical compound N#CC1=CC=CC=C1C1=NNC=C1 KRAWAGMBRSAXDJ-UHFFFAOYSA-N 0.000 description 1
- SRXDFBREVCVOBO-UHFFFAOYSA-N 2-(3-carboxyphenyl)-4-(4-propan-2-ylphenyl)furan-3-carboxylic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=COC(C=2C=C(C=CC=2)C(O)=O)=C1C(O)=O SRXDFBREVCVOBO-UHFFFAOYSA-N 0.000 description 1
- KRVGXFREOJHJAX-UHFFFAOYSA-N 2-bromo-1-(4-methylphenyl)ethanone Chemical compound CC1=CC=C(C(=O)CBr)C=C1 KRVGXFREOJHJAX-UHFFFAOYSA-N 0.000 description 1
- WLRIUCQUMKJOGT-UHFFFAOYSA-N 2-bromo-1-(4-pyrrolidin-1-ylphenyl)ethanone Chemical compound C1=CC(C(=O)CBr)=CC=C1N1CCCC1 WLRIUCQUMKJOGT-UHFFFAOYSA-N 0.000 description 1
- WJAXXWSZNSFVNG-UHFFFAOYSA-N 2-bromoethanamine;hydron;bromide Chemical compound [Br-].[NH3+]CCBr WJAXXWSZNSFVNG-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- UQVCPKNHQRKCGJ-UHFFFAOYSA-N 2-fluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=CC=CC=C1F UQVCPKNHQRKCGJ-UHFFFAOYSA-N 0.000 description 1
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
- IYELGEUXPAPULN-UHFFFAOYSA-N 2-hydroxybenzenecarboximidamide Chemical class NC(=N)C1=CC=CC=C1O IYELGEUXPAPULN-UHFFFAOYSA-N 0.000 description 1
- LRKBACPCJTXJNF-UHFFFAOYSA-N 2-propan-2-ylbenzonitrile Chemical compound CC(C)C1=CC=CC=C1C#N LRKBACPCJTXJNF-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- CCABKDOCJKPWOO-UHFFFAOYSA-N 2h-tetrazol-5-yl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC=1N=NNN=1 CCABKDOCJKPWOO-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- RYSMHWILUNYBFW-GRIPGOBMSA-N 3'-amino-3'-deoxy-N(6),N(6)-dimethyladenosine Chemical compound C1=NC=2C(N(C)C)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](N)[C@H]1O RYSMHWILUNYBFW-GRIPGOBMSA-N 0.000 description 1
- ABFYEILPZWAIBN-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.CN(C)CCCN=C=N ABFYEILPZWAIBN-UHFFFAOYSA-N 0.000 description 1
- DMRHRPXKVXWLCH-UHFFFAOYSA-N 3-[2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(C=2C=C(C=CC=2)C(O)=O)=CO1 DMRHRPXKVXWLCH-UHFFFAOYSA-N 0.000 description 1
- YUZRGKJBEOAQKN-UHFFFAOYSA-N 3-[3-oxo-3-(4-propan-2-ylphenyl)propanoyl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C(=O)CC(=O)C1=CC=CC(C(O)=O)=C1 YUZRGKJBEOAQKN-UHFFFAOYSA-N 0.000 description 1
- PMUOTCOMHRVNLI-UHFFFAOYSA-N 3-[5-(4-propan-2-ylphenyl)-1,3-thiazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=CN=C(C=2C=C(C=CC=2)C(O)=O)S1 PMUOTCOMHRVNLI-UHFFFAOYSA-N 0.000 description 1
- AQCGUGGLUCBCJC-UHFFFAOYSA-N 3-[5-[4-(3-methylphenyl)phenyl]-1,3,4-oxadiazol-2-yl]benzoic acid Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)C=2OC(=NN=2)C=2C=C(C=CC=2)C(O)=O)=C1 AQCGUGGLUCBCJC-UHFFFAOYSA-N 0.000 description 1
- CHZPJUSFUDUEMZ-UHFFFAOYSA-N 3-acetylbenzoic acid Chemical compound CC(=O)C1=CC=CC(C(O)=O)=C1 CHZPJUSFUDUEMZ-UHFFFAOYSA-N 0.000 description 1
- FVUKYCZRWSQGAS-UHFFFAOYSA-N 3-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC(C(O)=O)=C1 FVUKYCZRWSQGAS-UHFFFAOYSA-N 0.000 description 1
- GYLKKXHEIIFTJH-UHFFFAOYSA-N 3-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1 GYLKKXHEIIFTJH-UHFFFAOYSA-N 0.000 description 1
- HOPNITFHNCUXTG-UHFFFAOYSA-N 3-ethoxycarbonylbenzoic acid Chemical compound CCOC(=O)C1=CC=CC(C(O)=O)=C1 HOPNITFHNCUXTG-UHFFFAOYSA-N 0.000 description 1
- WMZNGTSLFSJHMZ-UHFFFAOYSA-N 3-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=C1 WMZNGTSLFSJHMZ-UHFFFAOYSA-N 0.000 description 1
- VPLPNOJLQDWYBM-UHFFFAOYSA-N 4-[5-(2,4-difluorophenyl)-1,3-oxazol-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC=C(C=2C(=CC(F)=CC=2)F)O1 VPLPNOJLQDWYBM-UHFFFAOYSA-N 0.000 description 1
- DMRUGSQJUXTUNH-UHFFFAOYSA-N 4-[5-(4-propan-2-ylphenyl)-1,3,4-thiadiazol-2-yl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NN=C(C=2C=CC(=CC=2)C(O)=O)S1 DMRUGSQJUXTUNH-UHFFFAOYSA-N 0.000 description 1
- LPCGXCWXECLWQS-UHFFFAOYSA-N 4-[[(4-propan-2-ylbenzoyl)amino]carbamoyl]benzoic acid Chemical compound C1=CC(C(C)C)=CC=C1C(=O)NNC(=O)C1=CC=C(C(O)=O)C=C1 LPCGXCWXECLWQS-UHFFFAOYSA-N 0.000 description 1
- XWQVQSXLXAXOPJ-QNGMFEMESA-N 4-[[[6-[5-chloro-2-[[4-[[(2r)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]pyridin-4-yl]pyridin-2-yl]amino]methyl]oxane-4-carbonitrile Chemical compound C1CC(N[C@H](C)COC)CCC1NC1=CC(C=2N=C(NCC3(CCOCC3)C#N)C=CC=2)=C(Cl)C=N1 XWQVQSXLXAXOPJ-QNGMFEMESA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- REKQLYUAUXYJSZ-UHFFFAOYSA-N 4-methoxybenzohydrazide Chemical compound COC1=CC=C(C(=O)NN)C=C1 REKQLYUAUXYJSZ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ZRVXDEFJKAAGGH-UHFFFAOYSA-N 4-propan-2-ylbenzohydrazide Chemical compound CC(C)C1=CC=C(C(=O)NN)C=C1 ZRVXDEFJKAAGGH-UHFFFAOYSA-N 0.000 description 1
- LBSYWDTVBUZMCM-UHFFFAOYSA-N 4-propan-2-ylbenzoyl chloride Chemical compound CC(C)C1=CC=C(C(Cl)=O)C=C1 LBSYWDTVBUZMCM-UHFFFAOYSA-N 0.000 description 1
- XYUFQWDLRLHUPB-UHFFFAOYSA-N 4-tert-butylbenzohydrazide Chemical compound CC(C)(C)C1=CC=C(C(=O)NN)C=C1 XYUFQWDLRLHUPB-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- KRWOCNIKEHCKKI-UHFFFAOYSA-N 5-(4-propan-2-ylphenyl)-1,3,4-oxathiazol-2-one Chemical compound C1=CC(C(C)C)=CC=C1C1=NSC(=O)O1 KRWOCNIKEHCKKI-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 108700040618 BRCA1 Genes Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 108700010154 BRCA2 Genes Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 1
- 102100028471 Eosinophil peroxidase Human genes 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 102100027270 Etoposide-induced protein 2.4 homolog Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 101001057564 Homo sapiens Etoposide-induced protein 2.4 homolog Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101000891649 Homo sapiens Transcription elongation factor A protein-like 1 Proteins 0.000 description 1
- 101100156155 Human papillomavirus type 16 E7 gene Proteins 0.000 description 1
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000596402 Mus musculus Neuronal vesicle trafficking-associated protein 1 Proteins 0.000 description 1
- 101000800539 Mus musculus Translationally-controlled tumor protein Proteins 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 102000007530 Neurofibromin 1 Human genes 0.000 description 1
- 108010085793 Neurofibromin 1 Proteins 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108020003217 Nuclear RNA Proteins 0.000 description 1
- 102000043141 Nuclear RNA Human genes 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- 108090000279 Peptidyltransferases Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 1
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108700025701 Retinoblastoma Genes Proteins 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 1
- 102000006308 Sarcoglycans Human genes 0.000 description 1
- 108010083379 Sarcoglycans Proteins 0.000 description 1
- 101000781972 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Protein wos2 Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 101001009610 Toxoplasma gondii Dense granule protein 5 Proteins 0.000 description 1
- 102100040250 Transcription elongation factor A protein-like 1 Human genes 0.000 description 1
- 101710102803 Tumor suppressor ARF Proteins 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 102100035071 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 102000040856 WT1 Human genes 0.000 description 1
- 108700020467 WT1 Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- ISXSJGHXHUZXNF-LXZPIJOJSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate;hydrochloride Chemical compound Cl.C1C=C2C[C@@H](OC(=O)NCCN(C)C)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 ISXSJGHXHUZXNF-LXZPIJOJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 229910052789 astatine Inorganic materials 0.000 description 1
- RYXHOMYVWAEKHL-UHFFFAOYSA-N astatine atom Chemical compound [At] RYXHOMYVWAEKHL-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000037429 base substitution Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WGNZRLMOMHJUSP-UHFFFAOYSA-N benzotriazol-1-yloxy(tripyrrolidin-1-yl)phosphanium Chemical compound C1CCCN1[P+](N1CCCC1)(N1CCCC1)ON1C2=CC=CC=C2N=N1 WGNZRLMOMHJUSP-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 1
- 229960002129 cefixime Drugs 0.000 description 1
- 229960002580 cefprozil Drugs 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- AVGYWQBCYZHHPN-CYJZLJNKSA-N cephalexin monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 AVGYWQBCYZHHPN-CYJZLJNKSA-N 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- XJKKCLQTZOSEDY-UHFFFAOYSA-N cyano benzoate Chemical compound N#COC(=O)C1=CC=CC=C1 XJKKCLQTZOSEDY-UHFFFAOYSA-N 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- DVIOWQGCUPHVBA-UHFFFAOYSA-N diazonio-[2-(3-methoxycarbonylphenyl)-2-oxoethyl]azanide Chemical compound COC(=O)C1=CC=CC(C(=O)CN=[N+]=[N-])=C1 DVIOWQGCUPHVBA-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 238000011833 dog model Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 230000000432 effect on mutation Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- OZWSHPFNEYQJSN-UHFFFAOYSA-N ethyl 3-(2-bromoacetyl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C(=O)CBr)=C1 OZWSHPFNEYQJSN-UHFFFAOYSA-N 0.000 description 1
- MEVWYHJOGPAXDC-UHFFFAOYSA-N ethyl 3-(2-trimethylsilylethynyl)benzoate Chemical compound CCOC(=O)C1=CC=CC(C#C[Si](C)(C)C)=C1 MEVWYHJOGPAXDC-UHFFFAOYSA-N 0.000 description 1
- PJQMLHLKGAZYQN-UHFFFAOYSA-N ethyl 3-[3-(4-propan-2-ylphenyl)-1,2,4-thiadiazol-5-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SN=C(N=2)C=2C=CC(=CC=2)C(C)C)=C1 PJQMLHLKGAZYQN-UHFFFAOYSA-N 0.000 description 1
- KJFSDCZVCOSTEN-UHFFFAOYSA-N ethyl 3-[4-(4-propan-2-ylphenyl)-1,3-thiazol-2-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC=C(N=2)C=2C=CC(=CC=2)C(C)C)=C1 KJFSDCZVCOSTEN-UHFFFAOYSA-N 0.000 description 1
- KCHHOBITKTWIFA-UHFFFAOYSA-N ethyl 3-[5-(4-propan-2-ylphenyl)thiophen-2-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(C=2SC(=CC=2)C=2C=CC(=CC=2)C(C)C)=C1 KCHHOBITKTWIFA-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 150000002244 furazanes Chemical class 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 238000011553 hamster model Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003566 hemangioblast Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.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 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- YPJRHEKCFKOVRT-UHFFFAOYSA-N lerociclib Chemical compound C1CN(C(C)C)CCN1C(C=N1)=CC=C1NC1=NC=C(C=C2N3C4(CCCCC4)CNC2=O)C3=N1 YPJRHEKCFKOVRT-UHFFFAOYSA-N 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- JBVNBBXAMBZTMQ-CEGNMAFCSA-N megestrol Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 JBVNBBXAMBZTMQ-CEGNMAFCSA-N 0.000 description 1
- 229960001786 megestrol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DVWRQSDGGLBVHA-UHFFFAOYSA-N methyl 3-(2-aminoacetyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)CN)=C1 DVWRQSDGGLBVHA-UHFFFAOYSA-N 0.000 description 1
- XHDHEDITROOBDC-UHFFFAOYSA-N methyl 3-(2h-tetrazol-5-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C2=NNN=N2)=C1 XHDHEDITROOBDC-UHFFFAOYSA-N 0.000 description 1
- IILHNVRSXRFFIY-UHFFFAOYSA-N methyl 3-(c-methoxycarbonimidoyl)benzoate;hydrochloride Chemical compound Cl.COC(=N)C1=CC=CC(C(=O)OC)=C1 IILHNVRSXRFFIY-UHFFFAOYSA-N 0.000 description 1
- ULDBARNRUJDALC-UHFFFAOYSA-N methyl 3-[2-(4-propan-2-ylphenyl)-1h-imidazol-5-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2NC(=NC=2)C=2C=CC(=CC=2)C(C)C)=C1 ULDBARNRUJDALC-UHFFFAOYSA-N 0.000 description 1
- LVJZFJZVRYHEAC-UHFFFAOYSA-N methyl 3-[4-oxo-4-(4-propan-2-ylphenyl)butanoyl]benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)CCC(=O)C=2C=CC(=CC=2)C(C)C)=C1 LVJZFJZVRYHEAC-UHFFFAOYSA-N 0.000 description 1
- CXNDVRLZAHECLS-UHFFFAOYSA-N methyl 3-[5-(4-bromophenyl)-1,3,4-oxadiazol-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NN=2)C=2C=CC(Br)=CC=2)=C1 CXNDVRLZAHECLS-UHFFFAOYSA-N 0.000 description 1
- UVSBCUAQEZINCQ-UHFFFAOYSA-N methyl 3-formylbenzoate Chemical compound COC(=O)C1=CC=CC(C=O)=C1 UVSBCUAQEZINCQ-UHFFFAOYSA-N 0.000 description 1
- FVLCZQXNKHDJHG-UHFFFAOYSA-N methyl 4-[5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NN=C(C=2C=C(C=CC=2)[N+]([O-])=O)O1 FVLCZQXNKHDJHG-UHFFFAOYSA-N 0.000 description 1
- WXHIJZFDFMDDGP-UHFFFAOYSA-N methyl 4-[5-(4-propan-2-ylphenyl)-1,3,4-thiadiazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NN=C(C=2C=CC(=CC=2)C(C)C)S1 WXHIJZFDFMDDGP-UHFFFAOYSA-N 0.000 description 1
- HARDABSUEYJOCS-UHFFFAOYSA-N methyl 4-[5-[3-[(4-methylphenyl)sulfonylamino]phenyl]-1,3,4-oxadiazol-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NN=C(C=2C=C(NS(=O)(=O)C=3C=CC(C)=CC=3)C=CC=2)O1 HARDABSUEYJOCS-UHFFFAOYSA-N 0.000 description 1
- KKZMIDYKRKGJHG-UHFFFAOYSA-N methyl 4-cyanobenzoate Chemical compound COC(=O)C1=CC=C(C#N)C=C1 KKZMIDYKRKGJHG-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000003274 myotonic effect Effects 0.000 description 1
- SJYQYOVTHISIKX-UHFFFAOYSA-N n,n-dimethylformamide;n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CN(C)C=O.CCN(C(C)C)C(C)C SJYQYOVTHISIKX-UHFFFAOYSA-N 0.000 description 1
- FZIVKDWRLLMSEJ-UHFFFAOYSA-N n-[(2-chlorophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=CC=CC=C1Cl FZIVKDWRLLMSEJ-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([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
- 229920001206 natural gum Polymers 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical class NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 229940121367 non-opioid analgesics Drugs 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000020943 pineal parenchymal cell neoplasm Diseases 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 230000026447 protein localization Effects 0.000 description 1
- 239000000649 purine antagonist Substances 0.000 description 1
- 239000003790 pyrimidine antagonist Substances 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000003571 reporter gene assay Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 101150079354 rho gene Proteins 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 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
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000008753 synovium neoplasm Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000012863 translational readthrough Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- ZCPSWAFANXCCOT-UHFFFAOYSA-N trichloromethanesulfonyl chloride Chemical compound ClC(Cl)(Cl)S(Cl)(=O)=O ZCPSWAFANXCCOT-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/24—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to three ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/107—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with two aryl or substituted aryl radicals attached in positions 2 and 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
- C07F9/65306—Five-membered rings containing two nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Psychology (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61767004P | 2004-10-13 | 2004-10-13 | |
| US61763304P | 2004-10-13 | 2004-10-13 | |
| US61763404P | 2004-10-13 | 2004-10-13 | |
| US61765504P | 2004-10-13 | 2004-10-13 | |
| US61765304P | 2004-10-13 | 2004-10-13 | |
| US62417004P | 2004-11-03 | 2004-11-03 | |
| PCT/US2005/036673 WO2006044456A1 (en) | 2004-10-13 | 2005-10-13 | Compounds for nonsense suppression, and methods for their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008515985A true JP2008515985A (ja) | 2008-05-15 |
| JP2008515985A5 JP2008515985A5 (enExample) | 2008-12-11 |
Family
ID=35517967
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007536865A Pending JP2008515990A (ja) | 2004-10-13 | 2005-10-13 | ナンセンス抑制のための化合物およびその使用方法 |
| JP2007536837A Pending JP2008515985A (ja) | 2004-10-13 | 2005-10-13 | ナンセンス抑制の化合物とその使用方法 |
| JP2007536867A Pending JP2008515992A (ja) | 2004-10-13 | 2005-10-13 | 体細胞変異に起因する疾患の阻止/治療用医薬を製造するための規定化合物の使用 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007536865A Pending JP2008515990A (ja) | 2004-10-13 | 2005-10-13 | ナンセンス抑制のための化合物およびその使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007536867A Pending JP2008515992A (ja) | 2004-10-13 | 2005-10-13 | 体細胞変異に起因する疾患の阻止/治療用医薬を製造するための規定化合物の使用 |
Country Status (11)
| Country | Link |
|---|---|
| US (10) | US9611230B2 (enExample) |
| EP (13) | EP2402323A3 (enExample) |
| JP (3) | JP2008515990A (enExample) |
| KR (3) | KR20070065429A (enExample) |
| AU (3) | AU2005295778A1 (enExample) |
| BR (2) | BRPI0516110A (enExample) |
| CA (5) | CA2583159A1 (enExample) |
| IL (3) | IL182459A0 (enExample) |
| MX (3) | MX2007004487A (enExample) |
| SG (2) | SG156640A1 (enExample) |
| WO (5) | WO2006044502A2 (enExample) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011525534A (ja) * | 2008-06-24 | 2011-09-22 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Gタンパク質共役受容体を調節するための化合物および方法 |
| JP2017537967A (ja) * | 2014-12-17 | 2017-12-21 | キングス カレッジ ロンドン | レチノイン酸受容体ベータ(RARβ)アゴニストとしてのビシクロヘテロアリール−ヘテロアリール−安息香酸化合物 |
| JP2018505860A (ja) * | 2014-12-19 | 2018-03-01 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 新規化合物、その合成方法、並びに医薬品及び化粧品におけるその使用 |
| JP2018527325A (ja) * | 2015-07-24 | 2018-09-20 | シンジェンタ パーティシペーションズ アーゲー | 硫黄含有置換基を有する殺有害生物的に活性な1,2,4−トリアゾール誘導体 |
| JP2020523390A (ja) * | 2017-06-14 | 2020-08-06 | トレベナ・インコーポレイテッドTrevena, Inc. | S1p1活性を調節するための化合物およびその使用法 |
| CN112074897A (zh) * | 2018-03-29 | 2020-12-11 | 艾克斯普罗工程股份公司 | 用于产生高振幅的压力波的设备和方法 |
| WO2022168962A1 (ja) * | 2021-02-04 | 2022-08-11 | 国立大学法人九州大学 | Il-31産生抑制剤、及びそれを含有する医薬組成物 |
| US11884655B2 (en) | 2019-11-19 | 2024-01-30 | Trevena, Inc. | Compounds and methods of preparing compounds S1P1 modulators |
Families Citing this family (114)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003252136A1 (en) | 2002-07-24 | 2004-02-09 | Ptc Therapeutics, Inc. | METHODS FOR IDENTIFYING SMALL MOLEDULES THAT MODULATE PREMATURE TRANSLATION TERMINATION AND NONSENSE MEDIATED mRNA DECAY |
| DK3549936T3 (da) | 2003-04-11 | 2021-07-12 | Ptc Therapeutics Inc | 1,2,4-oxadiazol-benzoesyreforbindelse og dens anvendelse til nonsense-undertrykkelse og behandlingen af sygdom |
| EP2402323A3 (en) * | 2004-10-13 | 2012-05-30 | PTC Therapeutics, Inc. | Pyrazole or triazole compounds and their use for the manufacture of a medicament for treating somatic mutation-related diseases |
| WO2007042543A2 (en) * | 2005-10-14 | 2007-04-19 | Neurosearch A/S | Imidazole derivatives and their use for modulating the gaba-a receptor complex |
| US20090304641A1 (en) | 2005-10-17 | 2009-12-10 | Children's Hospital Boston | Methods and Compositions for Regulating Gene Expression |
| EP1986633B1 (en) | 2006-02-10 | 2014-07-30 | Summit Corporation Plc | Treatment of duchenne muscular dystrophy |
| RU2462246C2 (ru) * | 2006-03-30 | 2012-09-27 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы получения функционального белка из днк, имеющей нонсенс-мутацию, и лечения нарушений, ассоциированных с ней |
| ES2882684T3 (es) | 2006-04-07 | 2021-12-02 | Vertex Pharma | Preparación de moduladores de transportadores del casete de unión a ATP |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| PL2076501T3 (pl) * | 2006-09-25 | 2016-06-30 | Ptc Therapeutics Inc | Postacie krystaliczne kwasu 3-[5-(2-fluorofenylo)[1,2,4]oksadiazol-3-ilo]-benzoesowego |
| KR100858357B1 (ko) * | 2006-10-02 | 2008-09-11 | (주) 디지탈바이오텍 | 벤조퓨란계 유도체 화합물을 유효성분으로 함유하는인지기능 장애의 예방 및 치료용 조성물 |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| WO2008157407A2 (en) * | 2007-06-13 | 2008-12-24 | University Of Virginia Patent Foundation | Thiadiazole, oxadiazole and triazole derivatives for treating leukemia |
| LT2170396T (lt) | 2007-08-03 | 2017-03-10 | Summit (Oxford) Limited | Vaistų deriniai, skirti diušeno raumenų distrofijos gydymui |
| EP2211956A4 (en) * | 2007-10-10 | 2014-07-09 | Parion Sciences Inc | DISPOSAL OF OSMOLYTES WITH A NOSE CANNULA |
| EP2578571B1 (en) | 2007-11-16 | 2015-09-16 | Vertex Pharmaceuticals Incorporated | Isoquinoline modulators of ATP-binding cassette transporters |
| CN103626744B (zh) | 2007-12-07 | 2016-05-11 | 沃泰克斯药物股份有限公司 | 3-(6-(1-(2,2-二氟苯并[d][1,3]间二氧杂环戊烯-5-基)环丙烷甲酰氨基)-3-甲基吡啶-2-基)苯甲酸的固体形式 |
| PT2615085E (pt) | 2008-03-31 | 2015-10-09 | Vertex Pharma | Derivados piridilo como moduladores cftr |
| JP5369854B2 (ja) | 2008-04-21 | 2013-12-18 | 住友化学株式会社 | 有害節足動物防除組成物および縮合複素環化合物 |
| ES2554772T3 (es) | 2008-05-30 | 2015-12-23 | Merck Sharp & Dohme Corp. | Azabenzoxazoles sustituidos novedosos |
| TW201000099A (en) | 2008-06-20 | 2010-01-01 | Amgen Inc | S1P1 receptor agonists and use thereof |
| NZ595819A (en) * | 2009-04-02 | 2013-02-22 | Merck Serono Sa | DIHYDROOROTATE DEHYDROGENASE INHIBITORS; benzimidazole-4-carboxylic acid |
| EP2467362A4 (en) * | 2009-08-17 | 2013-06-26 | Brigham & Womens Hospital | Phosphatidylcholine TRANSFER PROTEIN INHIBITORS |
| CN103947645B (zh) | 2009-10-12 | 2016-07-06 | 拜尔农作物科学股份公司 | 作为杀虫剂的1-(吡啶-3-基)-吡唑和1-(嘧啶-5-基)-吡唑 |
| WO2011085269A1 (en) * | 2010-01-08 | 2011-07-14 | Selexagen Therapeutics, Inc. | Raf kinase inhibitors |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| ES2845449T3 (es) | 2010-03-25 | 2021-07-26 | Vertex Pharma | Dispersión sólida de forma amorfa de (R)-1(2,2-difluorobenzo[d][1,3]dioxol-5-il)-N-(1-(2,3-dihidroxipropil)-6-fluoro-2(1-hidroxi-2-metilpropan-2-il)-1h-indol-5il)-ciclopropanocarboxamida |
| EP2555755B2 (en) | 2010-04-07 | 2019-07-10 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyriodin-2-yl)benzoic acid and administration thereof |
| AR081069A1 (es) | 2010-04-07 | 2012-06-06 | Vertex Pharma | Formas solidas del acido 3-(6-(1-(2,2-difluorbenzo[d][1,3]dioxol-5-il)ciclopropancarboxamido)-3-metilpiridin-2-il)benzoico |
| RU2569678C2 (ru) | 2010-04-22 | 2015-11-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способ получения циклоалкилкарбоксамидо-индольных соединений |
| KR101799429B1 (ko) * | 2010-05-03 | 2017-11-21 | 에스케이바이오팜 주식회사 | 신경 세포 사멸 또는 신경 퇴화를 억제하기 위한 약학적 조성물 |
| US8563593B2 (en) | 2010-06-08 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Formulations of (R)-1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide |
| CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| CA2808501A1 (en) | 2010-08-23 | 2012-03-01 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition of (r)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihydroxy propyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide and administration therof |
| EP3431485B2 (en) | 2010-10-01 | 2024-09-04 | ModernaTX, Inc. | Engineered nucleic acids and methods of use thereof |
| WO2012135805A2 (en) | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
| US8945605B2 (en) | 2011-06-07 | 2015-02-03 | Parion Sciences, Inc. | Aerosol delivery systems, compositions and methods |
| US8778383B2 (en) | 2011-06-07 | 2014-07-15 | Parion Sciences, Inc. | Methods of treatment |
| AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| EP2763701B1 (en) | 2011-10-03 | 2018-12-19 | Moderna Therapeutics, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
| US9254291B2 (en) | 2011-11-08 | 2016-02-09 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| KR20140102759A (ko) | 2011-12-16 | 2014-08-22 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물 |
| SMT201900451T1 (it) | 2012-01-25 | 2019-11-13 | Vertex Pharma | Formulazioni di acido 3-(6-(1-(2,2-difluorobenzo[d][1,3]diossol-5-il) ciclopropancarbossammido)-3-metilpiridin-2-il)benzoico |
| KR101452235B1 (ko) * | 2012-02-03 | 2014-10-22 | 서울대학교산학협력단 | 신규한 피리미딘계 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 포함하는 rage 수용체 관련 질환의 예방 또는 치료용 약학적 조성물 |
| US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
| US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
| DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
| AU2013243949A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
| US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
| EP2841428B1 (en) | 2012-04-24 | 2018-08-22 | Vertex Pharmaceuticals Incorporated | Dna-pk inhibitors |
| DK2855435T3 (en) | 2012-05-29 | 2018-07-16 | Parion Sciences Inc | DENDRIMER-LIKE AMINOAMIDES WITH SODIUM CHANNEL BLOCKING ACTIVITY FOR THE TREATMENT OF DRY EYES AND OTHER MILK DISEASES |
| US9012496B2 (en) | 2012-07-16 | 2015-04-21 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof |
| TWI736768B (zh) | 2012-11-02 | 2021-08-21 | 美商維泰克斯製藥公司 | 治療cftr介導疾病之醫藥組合物 |
| CA2892529C (en) | 2012-11-26 | 2023-04-25 | Moderna Therapeutics, Inc. | Terminally modified rna |
| ES2834959T3 (es) | 2012-12-06 | 2021-06-21 | Celgene Quanticel Res Inc | Inhibidores de histona desmetilasa |
| ES2674665T3 (es) | 2012-12-17 | 2018-07-03 | Parion Sciences, Inc. | Compuestos de 3,5-diamino-6-cloro-N-(N-(4-fenilbutilo)carbamimidoilo)-pirazina-2-carboxamida |
| US9029382B2 (en) | 2012-12-17 | 2015-05-12 | Parion Sciences, Inc. | 3,5-diamino-6-chloro-N-(N-(4-phenylbutyl)carbamimidoyl) pyrazine-2-carboxamide compounds |
| BR112015014349A2 (pt) | 2012-12-17 | 2017-07-11 | Parion Sciences Inc | derivados de cloro-pirazina carboxamida úteis para o tratamento de doenças favorecidas por hidratação mucosa insuficiente |
| WO2014159690A1 (en) | 2013-03-12 | 2014-10-02 | Vertex Pharmaceuticals Incorporated | Dna-pk inhibitors |
| US9376401B2 (en) * | 2013-03-13 | 2016-06-28 | Dow Agrosciences Llc | Preparation of 1,3-(substituted-diaryl)-1,2,4-triazoles and intermediates therefrom |
| US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
| BR112015021559A8 (pt) | 2013-03-15 | 2019-11-12 | Monsanto Technology Llc | compostos de azóis n-,c-dissubstituídos, composição nematicida aquosa, sementes e métodos para controlar nematódeos indesejados e para controlar ou prevenir uma infestação de nematódeos em um animal". |
| EP2970249A4 (en) * | 2013-03-15 | 2017-03-15 | Discoverybiomed Inc. | Coumarin derivatives and methods of use in treating hyperproliferative diseases |
| AU2014240026B2 (en) * | 2013-03-15 | 2018-06-14 | Discoverybiomed, Inc. | Coumarin derivatives and methods of use in treating cystic fibrosis, chronic obstructive pulmonary disease, and misfolded protein disorders |
| US10023626B2 (en) | 2013-09-30 | 2018-07-17 | Modernatx, Inc. | Polynucleotides encoding immune modulating polypeptides |
| EA201690675A1 (ru) | 2013-10-03 | 2016-08-31 | Модерна Терапьютикс, Инк. | Полинуклеотиды, кодирующие рецептор липопротеинов низкой плотности |
| FR3011468B1 (fr) * | 2013-10-04 | 2015-12-04 | Inventiva | Utilisation de l'odiparcil dans le traitement d'une mucopolysaccharidose |
| US9611263B2 (en) | 2013-10-08 | 2017-04-04 | Calcimedica, Inc. | Compounds that modulate intracellular calcium |
| PL3424920T3 (pl) | 2013-10-17 | 2020-11-16 | Vertex Pharmaceuticals Incorporated | Kokryształy (S)-N-metylo-8-(1-((2'-metylo-4’,6'-dideutero-[4,5'-bipirymidyn]-6-ylo)amino)propan-2-ylo)chinolino-4-karboksyamidu i ich deuterowane pochodne jako inhibitory DNA-PK |
| CA3174516A1 (en) | 2014-03-06 | 2015-09-11 | Ptc Therapeutics, Inc. | Pharmaceutical compositions and salts of a 1,2,4-oxadiazole benzoic acid |
| PT3131582T (pt) | 2014-04-15 | 2018-10-08 | Vertex Pharma | Composições farmacêuticas para o tratamento de doenças mediadas pelo regulador de condutância transmembranar da fibrose quística |
| US20170210788A1 (en) | 2014-07-23 | 2017-07-27 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
| PT3203840T (pt) | 2014-10-06 | 2020-10-27 | Vertex Pharma | Moduladores do regulador da condutância transmembranar da fibrose quística |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| WO2016105491A1 (en) | 2014-12-23 | 2016-06-30 | Fgh Biotech | Compositions of fatostatin based heterocyclic compounds and uses thereof |
| TW201729807A (zh) | 2015-10-30 | 2017-09-01 | Ptc治療公司 | 用於治療癲癇的方法 |
| MX2018007527A (es) | 2015-12-22 | 2018-09-07 | Syngenta Participations Ag | Derivados de pirazol activos como pesticidas. |
| JP7304697B2 (ja) | 2015-12-23 | 2023-07-07 | ムーンショット ファーマ エルエルシー | 未成熟終止コドンのリードスルーを促進することにより免疫反応を誘発するための方法 |
| WO2017190086A1 (en) | 2016-04-29 | 2017-11-02 | Fgh Biotech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
| SI3730487T1 (sl) | 2016-06-13 | 2022-08-31 | Gilead Sciences, Inc. | Azetidinski derivati kot modulatorji FXR (NR1H4) |
| CA3252823A1 (en) | 2016-06-13 | 2025-02-25 | Gilead Sciences Inc | Fxr (nr1h4) modulating compounds |
| GB201610867D0 (en) | 2016-06-22 | 2016-08-03 | King S College London | Crystalline forms of a therapeutic compound and processes for their preparation |
| CA3036195A1 (en) | 2016-09-07 | 2018-03-15 | Fgh Biotech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
| WO2018064092A1 (en) | 2016-09-27 | 2018-04-05 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of dna-damaging agents and dna-pk inhibitors |
| WO2018118848A1 (en) * | 2016-12-20 | 2018-06-28 | Bristol-Myers Squibb Company | Compounds useful as immunomodulators |
| JP6906626B2 (ja) | 2017-03-28 | 2021-07-21 | ギリアード サイエンシーズ, インコーポレイテッド | 肝疾患を処置するための治療的組み合わせ |
| US11439623B2 (en) * | 2017-04-04 | 2022-09-13 | Case Western Reserve University | Method of modulating ribonucleotide reductase |
| US11786607B2 (en) | 2017-06-15 | 2023-10-17 | Modernatx, Inc. | RNA formulations |
| WO2018237326A1 (en) | 2017-06-22 | 2018-12-27 | 1AlMOONSHOT PHARMA LLC | Methods for treating cancer with compositions comprising amlexanox and immune modulators |
| WO2019040724A1 (en) * | 2017-08-23 | 2019-02-28 | The Regents Of The University Of Michigan | SMALL MYC INHIBITOR MOLECULES AND USES THEREOF |
| MX2020002348A (es) | 2017-08-31 | 2020-10-08 | Modernatx Inc | Métodos de elaboración de nanopartículas lipídicas. |
| EP3713934B1 (en) | 2017-11-23 | 2022-04-13 | Universita' degli Studi di Palermo | Oxadiazole derivatives for the treatment of genetic diseases due to nonsense mutations |
| WO2019124577A1 (ko) | 2017-12-20 | 2019-06-27 | 재단법인 경기도경제과학진흥원 | 트리아졸 유도체 및 이의 용도 |
| US12152242B2 (en) | 2018-04-23 | 2024-11-26 | The Curators Of The University Of Missouri | CRISPR therapy |
| US12090235B2 (en) | 2018-09-20 | 2024-09-17 | Modernatx, Inc. | Preparation of lipid nanoparticles and methods of administration thereof |
| US11225473B2 (en) | 2019-01-15 | 2022-01-18 | Gilead Sciences, Inc. | FXR (NR1H4) modulating compounds |
| EP3927683A1 (en) | 2019-02-19 | 2021-12-29 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
| CN114025847B (zh) * | 2019-03-26 | 2024-05-24 | 神经孔疗法股份有限公司 | 作为tlr信号传导的调节剂的化合物和组合物 |
| KR102663365B1 (ko) * | 2019-09-25 | 2024-05-08 | 한국원자력의학원 | 신규 트리플루오로메틸페닐피라졸 유도체를 유효성분으로 함유하는 암 예방 또는 치료용 조성물 |
| WO2021060888A2 (ko) * | 2019-09-25 | 2021-04-01 | 한국원자력의학원 | 신규 트리플루오로메틸페닐피라졸 유도체를 유효성분으로 함유하는 암 예방 또는 치료용 조성물 |
| BR112022011372A2 (pt) * | 2019-12-10 | 2022-08-23 | Univ Indiana Trustees | Inibidores de interação de proteína a de replicação (rpa)-dna |
| KR102847693B1 (ko) * | 2019-12-27 | 2025-08-18 | 서울대학교산학협력단 | 옥사디아졸 유도체를 포함하는 비만의 예방 또는 치료용 조성물 |
| EP3912628A1 (en) | 2020-05-20 | 2021-11-24 | Institut de Recherche en Semiochimie et Ethologie Appliquée | Nucleoside analogues to inhibit the main protease of a coronavirus |
| CN115594642B (zh) * | 2021-06-28 | 2024-12-27 | 广西医科大学 | 阿齐瑞格三氮唑衍生物及其抗乳腺癌用途 |
| EP4173485A1 (en) * | 2021-10-27 | 2023-05-03 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Protein aggregation inhibiting compounds for plant disease control |
| AU2023238460A1 (en) * | 2022-03-25 | 2024-10-31 | Vasthera Co., Ltd. | 3-phenylisoxazole derivative, and pharmaceutical composition for preventing or treating eye disease, containing same as active ingredient |
| EP4612139A1 (en) | 2022-11-03 | 2025-09-10 | Sentonix, Inc. | Selective ligands for tau aggregates |
| GB202300021D0 (en) * | 2023-01-03 | 2023-02-15 | Thirtyfivebio Ltd | Compounds |
| WO2025116596A1 (ko) * | 2023-11-29 | 2025-06-05 | 가천대학교 산학협력단 | 신규 화합물 및 이를 포함하는 안질환 예방 또는 치료용 조성물 |
| CN119144004B (zh) * | 2024-08-12 | 2025-10-28 | 兰州大学 | 一种m-hof材料及其制备方法和在氢氧根离子识别中的应用 |
Citations (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3679669A (en) * | 1970-09-23 | 1972-07-25 | Ciba Geigy Ag | Phenyl-1,3,4-oxdiazole compounds |
| US3882138A (en) * | 1971-08-09 | 1975-05-06 | Uniroyal Inc | Oxazole and oxadiazole benzoic acid derivatives as herbicides |
| US3964896A (en) * | 1971-08-09 | 1976-06-22 | Uniroyal, Inc. | Oxadiazole benzoic acid derivatives as herbicides |
| US4035175A (en) * | 1974-07-29 | 1977-07-12 | Uniroyal Inc. | Method of retarding the growth of plants using certain oxadiazolyl, oxazolyl or thiadiazolyl benzoic acid derivatives |
| GB1494877A (en) * | 1975-01-10 | 1977-12-14 | Commw Scient Ind Res Org | Heterocyclic compounds and plant growth regulating compositions |
| US4210762A (en) * | 1978-08-17 | 1980-07-01 | Monsanto Company | 2[5-(3-Trifluoromethylphenyl)-1,3,4-oxadiazol-2-yl] benzoates |
| JPH06107615A (ja) * | 1991-01-30 | 1994-04-19 | Elf Atochem Sa | 2,5−ジアリール−1,3,4−オキサジアゾールヒドロキシエステル、ヒドロキシ酸及びアセトキシ酸、並びにそれらの合成方法 |
| WO1997034869A1 (en) * | 1996-03-18 | 1997-09-25 | Eisai Co., Ltd. | Fused-ring carboxylic acid derivatives |
| EP0838453A1 (en) * | 1995-06-30 | 1998-04-29 | Eisai Co., Ltd. | Heterocyclic carboxylic acid derivatives and drugs containing the same |
| DE19904389A1 (de) * | 1999-02-04 | 2000-08-10 | Bayer Ag | Verwendung von substituierten Isoxazolcarbonsäuren und Derivate und neue Stoffe |
| WO2001064646A2 (en) * | 2000-03-01 | 2001-09-07 | Tularik Inc. | Hydrazones and analogs as cholesterol lowering agents |
| US6291487B1 (en) * | 1996-09-30 | 2001-09-18 | Otsuka Pharmaceutical Co., Ltd. | Agent for inhibition of cytokine production and agent for inhibition of cell adhesion |
| JP2002536365A (ja) * | 1999-02-04 | 2002-10-29 | バイエル アクチェンゲゼルシャフト | 貧血と闘うのに使用される置換ピラゾールカルボン酸 |
| JP2003081832A (ja) * | 2001-06-26 | 2003-03-19 | Takeda Chem Ind Ltd | レチノイド関連受容体機能調節剤 |
| WO2003027085A2 (en) * | 2001-09-26 | 2003-04-03 | Bayer Pharmaceuticals Corporation | 3-pyridyl or 4-isoquinolinyl thiazoles as c17,20 lyase inhibitors |
| JP2003517479A (ja) * | 1999-12-16 | 2003-05-27 | シェーリング コーポレイション | 置換イミダゾール神経ペプチドyy5レセプタアンタゴニスト |
| WO2003097047A1 (en) * | 2002-05-13 | 2003-11-27 | Eli Lilly And Company | Multicyclic compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes |
| WO2004014366A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Hetero biaryl derivatives as matrix metalloproteinase inhibitors |
| JP2004510697A (ja) * | 2000-05-22 | 2004-04-08 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | トリプターゼ阻害剤として使用するためのアリールメチルアミン誘導体 |
| WO2004072050A1 (en) * | 2003-02-14 | 2004-08-26 | Novartis Ag | Heterocyclic compounds useful as nurr-1 activators |
| WO2004091502A2 (en) * | 2003-04-11 | 2004-10-28 | Ptc Therapeutics, Inc. | 1,2,4-oxadiazole benzoic acid compounds |
| JP2006509896A (ja) * | 2002-12-30 | 2006-03-23 | ザ プロクター アンド ギャンブル カンパニー | ガラス製品腐食防止のために自動食器洗いにおいて使用される水溶性金属塩含有すすぎ補助組成物 |
| WO2006044503A2 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, use of these compounds for the manufacture of a medicament for treating somatic mutation-related diseases |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3153017A (en) * | 1961-06-29 | 1964-10-13 | Eastman Kodak Co | Nitrogen-containing linear polyesters from amino methyl cyclohexanol and dicarboxylic acids |
| CH522432A (de) * | 1967-02-07 | 1972-06-30 | Ciba Geigy Ag | Verwendung von v-Triazolen als Schutzmittel für nichttextile organische Substrate gegen UV-Strahlen |
| DE1938904A1 (de) | 1968-08-02 | 1970-02-05 | Innothera Lab Sa | 1-Phenylpyrrole |
| GB1248070A (en) | 1968-12-16 | 1971-09-29 | Science Union & Cie | Thiazolyl-benzoic acid derivatives and process for preparing them |
| US3803162A (en) | 1969-10-03 | 1974-04-09 | Sandoz Ltd | 7-triazolyl-3-phenylcoumarins |
| BE789948A (fr) | 1971-10-13 | 1973-04-11 | Sandoz Sa | Nouveaux derives du pyrazole, leur preparation et leur application comme medicaments |
| US3948937A (en) * | 1972-02-29 | 1976-04-06 | E. I. Du Pont De Nemours And Company | Pyrazole plant growth regulants |
| US3947263A (en) * | 1974-07-29 | 1976-03-30 | Uniroyal, Inc. | Plant growth regulants |
| US4038285A (en) * | 1975-06-25 | 1977-07-26 | E. I. Du Pont De Nemours And Company | 1-(2-carboxyaryl)-4-arylimidazoles and 1-(2-carboxyaryl)-3-aryl-1,2,4-triazoles |
| US4032644A (en) | 1975-12-29 | 1977-06-28 | Sandoz, Inc. | Isoxazolyl benzoic acids |
| DE2722331A1 (de) | 1976-05-18 | 1977-11-24 | Ricoh Kk | 1,3,4-oxadiazolderivate sowie diese enthaltende elektrophotographische aufzeichnungsmaterialien |
| US4166732A (en) * | 1977-05-12 | 1979-09-04 | Monsanto Company | Oxadiazol-5-yl-benzoates |
| US4140515A (en) * | 1977-05-12 | 1979-02-20 | Monsanto Company | Aryl-3-isoxazole benzoates as plant growth regulants and herbicides |
| US4135910A (en) * | 1977-05-12 | 1979-01-23 | Monsanto Company | Oxadiazol-3-yl-benzoates as plant growth regulants |
| US4268299A (en) * | 1978-08-17 | 1981-05-19 | Monsanto Company | Method and composition for plant growth regulation containing trifluoromethyl 1,3,4 oxadiazol benzoates |
| CA1125768A (en) * | 1978-10-31 | 1982-06-15 | Hoffmann-La Roche Limited | Benzoxazole derivatives |
| US4229204A (en) | 1978-12-04 | 1980-10-21 | Monsanto Company | Trifluoromethylphenyl isoxazolyl benzoates |
| JPS58177977A (ja) | 1982-04-09 | 1983-10-18 | Grelan Pharmaceut Co Ltd | 4−フエニルピラゾ−ル類 |
| SU1063100A1 (ru) * | 1982-04-22 | 1985-06-30 | Предприятие П/Я А-7850 | Жидкокристаллический материал дл электрооптических устройств |
| US4760066A (en) * | 1982-09-21 | 1988-07-26 | Wayne State University | Method for treating human tumor cell metastasis |
| US4546113A (en) * | 1983-04-14 | 1985-10-08 | Pfizer Inc. | Antiprotozoal diamidines |
| DD226883A1 (de) * | 1984-07-30 | 1985-09-04 | Neubauer T Paedagog Hochschule | Verfahren zur herstellung von 1,3-disubstituierten 5-alkoxy-1,2,4-triazolen und 1,2,4-triazolin-5-onen |
| US5436252A (en) * | 1986-12-19 | 1995-07-25 | Merrell Dow Pharmaceuticals Inc. | 5-aryl-3H-1,2,4-triazol-3-ones and their use in the treatment of neurodegenerative disorders |
| US5283187A (en) | 1987-11-17 | 1994-02-01 | Brown University Research Foundation | Cell culture-containing tubular capsule produced by co-extrusion |
| US4892538A (en) | 1987-11-17 | 1990-01-09 | Brown University Research Foundation | In vivo delivery of neurotransmitters by implanted, encapsulated cells |
| DE3819037A1 (de) * | 1988-06-04 | 1989-12-14 | Hoechst Ag | 2,4-disubstituierte oxazol-derivate, verfahren zu ihrer herstellung sowie ihre verwendung als therapiemittel gegen krankheiten, die durch rhinoviren verursacht werden |
| US5260451A (en) * | 1989-05-11 | 1993-11-09 | Merckle Gmbh | Substituted pyrrole compounds and use thereof in pharmaceutical compositions |
| US5022915A (en) * | 1990-03-01 | 1991-06-11 | Ici Americas Inc. | Substituted 2,4-diarylpyrimidines and their use as herbicides |
| SG86971A1 (en) | 1990-11-30 | 2002-03-19 | Teijin Ltd | 2-arylthiazole derivatives and pharmaceutical composition thereof |
| AU4528493A (en) | 1992-06-04 | 1994-01-04 | Regents Of The University Of California, The | In vivo gene therapy with intron-free sequence of interest |
| US5466823A (en) | 1993-11-30 | 1995-11-14 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides |
| IL112290A (en) * | 1994-01-12 | 1999-01-26 | Novartis Ag | Transformed aryl and the troiryl pyrimidines and herbicides containing them |
| US5521189A (en) * | 1994-05-06 | 1996-05-28 | The University Of Nc At Ch | Methods of treating pneumocystis carinii pneumonia |
| US5486534A (en) * | 1994-07-21 | 1996-01-23 | G. D. Searle & Co. | 3,4-substituted pyrazoles for the treatment of inflammation |
| MX9702531A (es) * | 1994-10-07 | 1997-06-28 | Fujisawa Pharmaceutical Co | Compuesto nuevo. |
| US5681746A (en) | 1994-12-30 | 1997-10-28 | Chiron Viagene, Inc. | Retroviral delivery of full length factor VIII |
| DE19536811A1 (de) | 1995-10-02 | 1997-04-03 | Basf Ag | Zwischenprodukte und Verfahren zur Herstellung von substituierten Salicylsäurederivaten als Pflanzenschutzmittel |
| DE19620041A1 (de) * | 1996-05-17 | 1998-01-29 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| TW467902B (en) | 1996-07-31 | 2001-12-11 | Bristol Myers Squibb Co | Diphenyl heterocycles as potassium channel modulators |
| WO1998015532A1 (en) | 1996-10-09 | 1998-04-16 | Novartis Ag | Solid phase synthesis of heterocyclic compounds |
| SK74999A3 (en) * | 1996-11-25 | 2000-02-14 | Procter & Gamble | 2-imidazolinylaminobenzoxazole compounds useful as alpha-2 adrenoceptor agonists |
| AU5802798A (en) | 1996-12-20 | 1998-07-17 | Human Genome Sciences, Inc. | Human oncogene induced secreted protein i |
| SI1023063T1 (en) * | 1997-10-06 | 2004-02-29 | Abbott Gmbh & Co. Kg | INDENO(1,2-c), NAPHTHO(1,2-c)- AND BENZO(6,7)CYCLOHEPTA(1,2-c)PYRAZOLE DERIVATIVES |
| ATE249217T1 (de) | 1997-10-06 | 2003-09-15 | Abbott Gmbh & Co Kg | Indeno(1,2-c)-,naphtho(1,2-c)-und benzo(6, 7)cyclohepta(1,2-c)pyrazolderivate |
| DE19816880A1 (de) | 1998-04-17 | 1999-10-21 | Boehringer Ingelheim Pharma | Neue Diphenyl-substituierte 5-Ring-Heterocyclen, Verfahren zu ihrer Herstellung sowie deren Verwendung als Arzneimittel |
| BR9907967A (pt) * | 1998-02-09 | 2000-10-17 | Fujisawa Pharmaceutical Co | Composto de polipeptideo, processo para sua preparação, composição farmacêutica compreendendo dito composto, e seu uso. |
| AU4005299A (en) * | 1998-05-19 | 1999-12-06 | Regents Of The University Of California, The | Thiazolidine and oxazolidine derivatives for the treatment of acute myocardial infarction and inhibition of cardiomyocyte apoptosis |
| US6262098B1 (en) | 1998-08-07 | 2001-07-17 | Chiron Corporation | Estrogen receptor modulators |
| US7729756B2 (en) | 2000-01-18 | 2010-06-01 | Siemens Aktiengesellschaft | Measurement system for examining a section of tissue on a patient and the use of a measurement system of this type |
| WO2001059100A2 (en) | 2000-02-11 | 2001-08-16 | Genentech, Inc. | Inhibitor of hepatocyte growth factor activator for use in modulation of angiogenesis and cardiovascularization |
| KR100858642B1 (ko) * | 2000-05-22 | 2008-09-17 | 아벤티스 파마슈티칼스 인크. | 트립타제 억제제로서 사용하기 위한 아릴메틸아민 유도체 |
| AU2002216649A1 (en) * | 2000-10-31 | 2002-05-15 | Lynn Bonham | Benzoxazole lpaat- beta inhibitors and uses thereof |
| PL369598A1 (en) * | 2001-02-21 | 2005-05-02 | Nps Pharmaceuticals, Inc. | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| AUPR362001A0 (en) | 2001-03-08 | 2001-04-05 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| JP2003026663A (ja) | 2001-05-09 | 2003-01-29 | Takeda Chem Ind Ltd | アゾール化合物、その製造法および用途 |
| EP1386915A4 (en) | 2001-05-09 | 2004-11-10 | Sumitomo Chem Takeda Agro Co | AZOL COMPOUNDS, METHOD FOR THE PRODUCTION AND USE THEREOF |
| WO2003000249A1 (en) * | 2001-06-26 | 2003-01-03 | Takeda Chemical Industries, Ltd. | Function regulator for retinoid relative receptor |
| DE10136066A1 (de) | 2001-07-25 | 2003-02-13 | Bayer Cropscience Ag | Tetrahydropyridazin-Derivate |
| WO2003016280A1 (en) * | 2001-08-13 | 2003-02-27 | Lion Bioscience Ag | Nr1h4 nuclear receptor binding compounds |
| JP4299139B2 (ja) * | 2001-12-18 | 2009-07-22 | メルク エンド カムパニー インコーポレーテッド | 代謝型グルタミン酸受容体−5のヘテロアリール置換トリアゾールモジュレータ |
| JP4286146B2 (ja) * | 2001-12-18 | 2009-06-24 | メルク エンド カムパニー インコーポレーテッド | メタボトロピックグルタミン酸受容体−5のヘテロアリール置換ピラゾール系調節剤 |
| US7371767B2 (en) | 2001-12-21 | 2008-05-13 | Merck & Co., Inc. | Heteroaryl substituted pyrrole modulators of metabotropic glutamate receptor-5 |
| NZ548796A (en) | 2002-05-15 | 2008-01-31 | Janssen Pharmaceutica Nv | N-substituted trycyclic 3-aminopyrazoles as PDFG receptor inhibitors |
| AU2003261237A1 (en) | 2002-07-24 | 2004-02-09 | Ptc Therapeutics, Inc. | Use of nucleoside compounds for nonsense suppression and the treatment of genetic diseases |
| EP1525185A1 (en) * | 2002-07-24 | 2005-04-27 | PTC Therapeutics, Inc. | Acetylamino benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
| ATE548354T1 (de) * | 2002-07-24 | 2012-03-15 | Ptc Therapeutics Inc | Ureido-substituierte benzoesäureverbindungen und ihre verwendung für die nonsense-suppression und behandlung von erkrankungen |
| CA2495285A1 (en) * | 2002-08-13 | 2004-02-19 | Merck Sharp & Dohme Limited | Phenylpyridazine derivatives as ligands for gaba receptors |
| US6967254B2 (en) * | 2002-09-09 | 2005-11-22 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| AU2003283597A1 (en) * | 2002-11-16 | 2004-06-15 | Oxford Glycosciences (Uk) Ltd | Benzoxazole, benzthiazole and benzimidazole acid derivatives and their use as heparanase inhibitors |
| DE602004021472D1 (en) | 2003-02-20 | 2009-07-23 | Smithkline Beecham Corp | Pyrimiidinverbindungen |
| US7320986B2 (en) | 2003-03-07 | 2008-01-22 | Abbott Labortories | Fused tri and tetra-cyclic pyrazole kinase inhibitors |
| CN1809559B (zh) | 2003-04-18 | 2010-06-02 | 记忆药物公司 | 作为磷酸二酯酶4抑制剂的吡唑衍生物 |
| BRPI0514553A (pt) | 2004-08-23 | 2008-06-17 | Lilly Co Eli | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, métodos para inibir o receptor de histamina h3 em um mamìfero, para o tratamento de um distúrbio do sistema nervoso, para o tratamento de obesidade e para o tratamento de um distúrbio ou doença, e, uso de um composto ou um sal do mesmo |
| WO2007059356A2 (en) | 2005-11-19 | 2007-05-24 | Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Furfurylidene- pyrazolidines and their use as inhibitors of ubiquitin e1 |
| EP2284154A1 (en) | 2009-07-29 | 2011-02-16 | Argon Pharma S.L. | Antitumor 1,2-diphenylpyrrole compounds and their preparation process |
-
2005
- 2005-10-13 EP EP10185139A patent/EP2402323A3/en not_active Withdrawn
- 2005-10-13 EP EP10185128.5A patent/EP2301536B1/en not_active Expired - Lifetime
- 2005-10-13 CA CA002583159A patent/CA2583159A1/en not_active Abandoned
- 2005-10-13 JP JP2007536865A patent/JP2008515990A/ja active Pending
- 2005-10-13 MX MX2007004487A patent/MX2007004487A/es unknown
- 2005-10-13 US US11/577,191 patent/US9611230B2/en not_active Expired - Fee Related
- 2005-10-13 EP EP10185130.1A patent/EP2311455B1/en not_active Expired - Lifetime
- 2005-10-13 US US11/577,192 patent/US7902235B2/en not_active Expired - Fee Related
- 2005-10-13 EP EP10185126.9A patent/EP2301538B1/en not_active Expired - Lifetime
- 2005-10-13 WO PCT/US2005/036761 patent/WO2006044502A2/en not_active Ceased
- 2005-10-13 EP EP10185137A patent/EP2316452A1/en not_active Withdrawn
- 2005-10-13 EP EP05804194A patent/EP1799207A2/en not_active Withdrawn
- 2005-10-13 JP JP2007536837A patent/JP2008515985A/ja active Pending
- 2005-10-13 AU AU2005295778A patent/AU2005295778A1/en not_active Abandoned
- 2005-10-13 WO PCT/US2005/037052 patent/WO2006044682A1/en not_active Ceased
- 2005-10-13 WO PCT/US2005/036762 patent/WO2006044503A2/en not_active Ceased
- 2005-10-13 US US11/577,189 patent/US9315467B2/en active Active
- 2005-10-13 EP EP05815159.8A patent/EP1815206B1/en not_active Expired - Lifetime
- 2005-10-13 SG SG200906828-9A patent/SG156640A1/en unknown
- 2005-10-13 US US11/577,177 patent/US9051342B2/en not_active Expired - Fee Related
- 2005-10-13 JP JP2007536867A patent/JP2008515992A/ja active Pending
- 2005-10-13 KR KR1020077010794A patent/KR20070065429A/ko not_active Withdrawn
- 2005-10-13 EP EP16163831.7A patent/EP3067053A1/en not_active Withdrawn
- 2005-10-13 CA CA002582885A patent/CA2582885A1/en not_active Abandoned
- 2005-10-13 BR BRPI0516110-0A patent/BRPI0516110A/pt not_active IP Right Cessation
- 2005-10-13 AU AU2005295727A patent/AU2005295727A1/en not_active Abandoned
- 2005-10-13 EP EP15168072.5A patent/EP2939674A1/en not_active Withdrawn
- 2005-10-13 CA CA002583971A patent/CA2583971A1/en not_active Abandoned
- 2005-10-13 MX MX2007004484A patent/MX2007004484A/es unknown
- 2005-10-13 EP EP10185133A patent/EP2363129A1/en not_active Withdrawn
- 2005-10-13 EP EP05807667A patent/EP1799659A1/en not_active Withdrawn
- 2005-10-13 EP EP05804171A patent/EP1812071A2/en not_active Withdrawn
- 2005-10-13 MX MX2007004479A patent/MX2007004479A/es unknown
- 2005-10-13 AU AU2005295730A patent/AU2005295730A1/en not_active Abandoned
- 2005-10-13 CA CA002583177A patent/CA2583177A1/en not_active Abandoned
- 2005-10-13 KR KR1020077010767A patent/KR20070067201A/ko not_active Withdrawn
- 2005-10-13 US US11/577,176 patent/US20080269191A1/en not_active Abandoned
- 2005-10-13 EP EP05807462A patent/EP1799212A2/en not_active Withdrawn
- 2005-10-13 KR KR1020077009154A patent/KR20070067165A/ko not_active Withdrawn
- 2005-10-13 WO PCT/US2005/036764 patent/WO2006044505A2/en not_active Ceased
- 2005-10-13 BR BRPI0515995-4A patent/BRPI0515995A/pt not_active IP Right Cessation
- 2005-10-13 SG SG200906829-7A patent/SG156641A1/en unknown
- 2005-10-13 WO PCT/US2005/036673 patent/WO2006044456A1/en not_active Ceased
- 2005-10-13 CA CA002583976A patent/CA2583976A1/en not_active Abandoned
-
2007
- 2007-04-11 IL IL182459A patent/IL182459A0/en unknown
- 2007-04-11 IL IL182461A patent/IL182461A0/en unknown
- 2007-04-11 IL IL182464A patent/IL182464A0/en unknown
-
2011
- 2011-03-07 US US13/042,456 patent/US8710031B2/en not_active Expired - Fee Related
-
2014
- 2014-04-28 US US14/263,478 patent/US9273076B2/en not_active Expired - Lifetime
-
2015
- 2015-06-08 US US14/733,615 patent/US20150274674A1/en not_active Abandoned
-
2016
- 2016-04-15 US US15/130,318 patent/US20160229818A1/en not_active Abandoned
-
2017
- 2017-03-31 US US15/475,240 patent/US20170204073A1/en not_active Abandoned
Patent Citations (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3679669A (en) * | 1970-09-23 | 1972-07-25 | Ciba Geigy Ag | Phenyl-1,3,4-oxdiazole compounds |
| US3882138A (en) * | 1971-08-09 | 1975-05-06 | Uniroyal Inc | Oxazole and oxadiazole benzoic acid derivatives as herbicides |
| US3964896A (en) * | 1971-08-09 | 1976-06-22 | Uniroyal, Inc. | Oxadiazole benzoic acid derivatives as herbicides |
| US4035175A (en) * | 1974-07-29 | 1977-07-12 | Uniroyal Inc. | Method of retarding the growth of plants using certain oxadiazolyl, oxazolyl or thiadiazolyl benzoic acid derivatives |
| GB1494877A (en) * | 1975-01-10 | 1977-12-14 | Commw Scient Ind Res Org | Heterocyclic compounds and plant growth regulating compositions |
| US4210762A (en) * | 1978-08-17 | 1980-07-01 | Monsanto Company | 2[5-(3-Trifluoromethylphenyl)-1,3,4-oxadiazol-2-yl] benzoates |
| JPH06107615A (ja) * | 1991-01-30 | 1994-04-19 | Elf Atochem Sa | 2,5−ジアリール−1,3,4−オキサジアゾールヒドロキシエステル、ヒドロキシ酸及びアセトキシ酸、並びにそれらの合成方法 |
| EP0838453A1 (en) * | 1995-06-30 | 1998-04-29 | Eisai Co., Ltd. | Heterocyclic carboxylic acid derivatives and drugs containing the same |
| WO1997034869A1 (en) * | 1996-03-18 | 1997-09-25 | Eisai Co., Ltd. | Fused-ring carboxylic acid derivatives |
| US6291487B1 (en) * | 1996-09-30 | 2001-09-18 | Otsuka Pharmaceutical Co., Ltd. | Agent for inhibition of cytokine production and agent for inhibition of cell adhesion |
| JP2002536365A (ja) * | 1999-02-04 | 2002-10-29 | バイエル アクチェンゲゼルシャフト | 貧血と闘うのに使用される置換ピラゾールカルボン酸 |
| DE19904389A1 (de) * | 1999-02-04 | 2000-08-10 | Bayer Ag | Verwendung von substituierten Isoxazolcarbonsäuren und Derivate und neue Stoffe |
| JP2003517479A (ja) * | 1999-12-16 | 2003-05-27 | シェーリング コーポレイション | 置換イミダゾール神経ペプチドyy5レセプタアンタゴニスト |
| WO2001064646A2 (en) * | 2000-03-01 | 2001-09-07 | Tularik Inc. | Hydrazones and analogs as cholesterol lowering agents |
| JP2004510697A (ja) * | 2000-05-22 | 2004-04-08 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | トリプターゼ阻害剤として使用するためのアリールメチルアミン誘導体 |
| JP2003081832A (ja) * | 2001-06-26 | 2003-03-19 | Takeda Chem Ind Ltd | レチノイド関連受容体機能調節剤 |
| WO2003027085A2 (en) * | 2001-09-26 | 2003-04-03 | Bayer Pharmaceuticals Corporation | 3-pyridyl or 4-isoquinolinyl thiazoles as c17,20 lyase inhibitors |
| WO2003097047A1 (en) * | 2002-05-13 | 2003-11-27 | Eli Lilly And Company | Multicyclic compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes |
| WO2004014366A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Hetero biaryl derivatives as matrix metalloproteinase inhibitors |
| JP2006509896A (ja) * | 2002-12-30 | 2006-03-23 | ザ プロクター アンド ギャンブル カンパニー | ガラス製品腐食防止のために自動食器洗いにおいて使用される水溶性金属塩含有すすぎ補助組成物 |
| WO2004072050A1 (en) * | 2003-02-14 | 2004-08-26 | Novartis Ag | Heterocyclic compounds useful as nurr-1 activators |
| WO2004091502A2 (en) * | 2003-04-11 | 2004-10-28 | Ptc Therapeutics, Inc. | 1,2,4-oxadiazole benzoic acid compounds |
| JP2006522826A (ja) * | 2003-04-11 | 2006-10-05 | ピーティーシー セラピューティクス,インコーポレーテッド | 1,2,4−オキサジアゾール安息香酸化合物ならびにナンセンス抑制及び疾患の治療のためのその使用 |
| WO2006044503A2 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, use of these compounds for the manufacture of a medicament for treating somatic mutation-related diseases |
| WO2006044502A2 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Pyrazole or triazole compounds and their use for the manufacture of a medicament for treating somatic mutation-related diseases |
| WO2006044505A2 (en) * | 2004-10-13 | 2006-04-27 | Ptc Therapeutics, Inc. | Compounds for nonsense suppression, and methods for their use |
Non-Patent Citations (4)
| Title |
|---|
| HIROYUKI YOSHIMURA ET AL., J. MED. CHEM., vol. 43, JPN6012004711, 2000, pages 2929 - 2937, ISSN: 0002134844 * |
| KOUICHI KIKUCHI ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 11, JPN6012004714, 2001, pages 1215 - 1218, ISSN: 0002134846 * |
| LAURENCE EYROLLES ET AL., J. MED. CHEM., vol. 37, JPN6012004713, 1994, pages 1508 - 1517, ISSN: 0002134845 * |
| NAOKI KOBAYASHI ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 12, JPN6012004716, 2002, pages 1747 - 1750, ISSN: 0002134847 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011525534A (ja) * | 2008-06-24 | 2011-09-22 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Gタンパク質共役受容体を調節するための化合物および方法 |
| JP2017537967A (ja) * | 2014-12-17 | 2017-12-21 | キングス カレッジ ロンドン | レチノイン酸受容体ベータ(RARβ)アゴニストとしてのビシクロヘテロアリール−ヘテロアリール−安息香酸化合物 |
| JP2018505860A (ja) * | 2014-12-19 | 2018-03-01 | ガルデルマ・リサーチ・アンド・デヴェロップメント | 新規化合物、その合成方法、並びに医薬品及び化粧品におけるその使用 |
| JP2018527325A (ja) * | 2015-07-24 | 2018-09-20 | シンジェンタ パーティシペーションズ アーゲー | 硫黄含有置換基を有する殺有害生物的に活性な1,2,4−トリアゾール誘導体 |
| JP2020523390A (ja) * | 2017-06-14 | 2020-08-06 | トレベナ・インコーポレイテッドTrevena, Inc. | S1p1活性を調節するための化合物およびその使用法 |
| JP7252908B2 (ja) | 2017-06-14 | 2023-04-05 | トレベナ・インコーポレイテッド | S1p1活性を調節するための化合物およびその使用法 |
| US11912693B2 (en) | 2017-06-14 | 2024-02-27 | Trevena, Inc. | Compounds for modulating S1P1 activity and methods of using the same |
| CN112074897A (zh) * | 2018-03-29 | 2020-12-11 | 艾克斯普罗工程股份公司 | 用于产生高振幅的压力波的设备和方法 |
| US11884655B2 (en) | 2019-11-19 | 2024-01-30 | Trevena, Inc. | Compounds and methods of preparing compounds S1P1 modulators |
| WO2022168962A1 (ja) * | 2021-02-04 | 2022-08-11 | 国立大学法人九州大学 | Il-31産生抑制剤、及びそれを含有する医薬組成物 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9611230B2 (en) | 1,3,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081014 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20081014 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081021 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120131 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120626 |