DK2655345T3 - Aryltriazole Compounds with Anti-tumor Effect - Google Patents
Aryltriazole Compounds with Anti-tumor Effect Download PDFInfo
- Publication number
- DK2655345T3 DK2655345T3 DK11805449.3T DK11805449T DK2655345T3 DK 2655345 T3 DK2655345 T3 DK 2655345T3 DK 11805449 T DK11805449 T DK 11805449T DK 2655345 T3 DK2655345 T3 DK 2655345T3
- Authority
- DK
- Denmark
- Prior art keywords
- phenyl
- isopropyl
- dihydroxy
- triazole
- ylmethyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 77
- 230000000259 anti-tumor effect Effects 0.000 title description 3
- -1 4- (morpholin-4-ylmethyl-phenyl) - [1,2,3] -triazol-1-yl Chemical group 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 29
- 206010028980 Neoplasm Diseases 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 229960001755 resorcinol Drugs 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000012298 atmosphere Substances 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- GRWUWTJRPDVUNR-UHFFFAOYSA-N 5-[4-[[2-(diethylamino)ethylamino]methyl]phenyl]-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C1=CC=C(CNCCN(CC)CC)C=C1 GRWUWTJRPDVUNR-UHFFFAOYSA-N 0.000 claims description 5
- 201000006474 Brain Ischemia Diseases 0.000 claims description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 claims description 4
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000003880 polar aprotic solvent Substances 0.000 claims description 4
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- AYTRRCUXJZHIPQ-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-[[(1-methylpiperidin-4-yl)amino]methyl]phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CNC1CCN(C)CC1 AYTRRCUXJZHIPQ-UHFFFAOYSA-N 0.000 claims description 3
- PNMRMEXSPUOBKG-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-[[2-(2-hydroxyethyl)piperidin-1-yl]methyl]phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCCCC1CCO PNMRMEXSPUOBKG-UHFFFAOYSA-N 0.000 claims description 3
- CAIJFEGIAAQWDA-UHFFFAOYSA-N 4-[5-(4-morpholin-4-ylanilino)triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC=2C=CC(=CC=2)N2CCOCC2)=C1O CAIJFEGIAAQWDA-UHFFFAOYSA-N 0.000 claims description 3
- ZJSCBXBMQFTBAY-UHFFFAOYSA-N 4-[5-[4-[(3-hydroxypiperidin-1-yl)methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CC(O)CCC3)=CC=2)=C1O ZJSCBXBMQFTBAY-UHFFFAOYSA-N 0.000 claims description 3
- GBUFUJGPAXHPDH-UHFFFAOYSA-N 4-[5-[4-[(4-benzylpiperazin-1-yl)methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCN(CC=4C=CC=CC=4)CC3)=CC=2)=C1O GBUFUJGPAXHPDH-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 210000003679 cervix uteri Anatomy 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 201000004792 malaria Diseases 0.000 claims description 3
- 208000037819 metastatic cancer Diseases 0.000 claims description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 230000001575 pathological effect Effects 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- NCROGRSEZXPSAB-FQEVSTJZSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-[[(3s)-3-(dimethylamino)pyrrolidin-1-yl]methyl]phenyl]-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CC[C@H](N(C)C)C1 NCROGRSEZXPSAB-FQEVSTJZSA-N 0.000 claims description 2
- ZSOQWPOVGAAMDL-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-(imidazol-1-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1C=CN=C1 ZSOQWPOVGAAMDL-UHFFFAOYSA-N 0.000 claims description 2
- SJDWGCMBVASEIX-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-(pyrrolidin-1-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCCC1 SJDWGCMBVASEIX-UHFFFAOYSA-N 0.000 claims description 2
- VSNXLVSDXQIPLA-UHFFFAOYSA-N 4-[5-[4-(diethylaminomethyl)phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=CC(CN(CC)CC)=CC=C1C1=CN=NN1C1=CC(C(C)C)=C(O)C=C1O VSNXLVSDXQIPLA-UHFFFAOYSA-N 0.000 claims description 2
- STXBIUJYMJSDOH-UHFFFAOYSA-N 4-[5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCN(C)CC3)=CC=2)=C1O STXBIUJYMJSDOH-UHFFFAOYSA-N 0.000 claims description 2
- DXTFENZEURBOIF-UHFFFAOYSA-N 4-propan-2-yl-6-[5-[4-(pyrrolidin-1-ylmethyl)phenyl]triazol-1-yl]benzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCCC3)=CC=2)=C1O DXTFENZEURBOIF-UHFFFAOYSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000009182 Parasitemia Diseases 0.000 claims description 2
- 208000030852 Parasitic disease Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 210000001508 eye Anatomy 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- JOMWZJLCZBJOBA-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-(morpholin-4-ylmethyl)cyclohexane-1-carboxamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C2CCC(CN3CCOCC3)CC2)=C1O JOMWZJLCZBJOBA-UHFFFAOYSA-N 0.000 claims description 2
- CPGIJQOIMPLUKZ-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-morpholin-4-ylbenzamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C=2C=CC(=CC=2)N2CCOCC2)=C1O CPGIJQOIMPLUKZ-UHFFFAOYSA-N 0.000 claims description 2
- TYEOLZSYLVSPBJ-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-piperidin-1-ylbenzamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C=2C=CC(=CC=2)N2CCCCC2)=C1O TYEOLZSYLVSPBJ-UHFFFAOYSA-N 0.000 claims description 2
- 210000003739 neck Anatomy 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000004303 peritoneum Anatomy 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 210000001519 tissue Anatomy 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
- 235000019687 Lamb Nutrition 0.000 claims 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
- 229920006063 Lamide® Polymers 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 1
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- 150000000185 1,3-diols Chemical class 0.000 claims 1
- GTODOEDLCNTSLG-UHFFFAOYSA-N 2h-triazole-4-carboxylic acid Chemical compound OC(=O)C1=CNN=N1 GTODOEDLCNTSLG-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 206010050389 Cerebral ataxia Diseases 0.000 claims 1
- 208000009829 Lewy Body Disease Diseases 0.000 claims 1
- 206010027406 Mesothelioma Diseases 0.000 claims 1
- 150000002009 diols Chemical class 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 229960005181 morphine Drugs 0.000 claims 1
- 201000000585 muscular atrophy Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 26
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 26
- 238000004440 column chromatography Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 23
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- KZFXDPOZDSLOHV-UHFFFAOYSA-N 1-azido-2,4-bis(phenylmethoxy)-5-propan-2-ylbenzene Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC(N=[N+]=[N-])=C1OCC1=CC=CC=C1 KZFXDPOZDSLOHV-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 150000000177 1,2,3-triazoles Chemical class 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 230000001143 conditioned effect Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- DCVWMMMKFZVEDP-UHFFFAOYSA-N 1-(cyclobutylmethyl)triazole-4-carboxylic acid Chemical compound N1=NC(C(=O)O)=CN1CC1CCC1 DCVWMMMKFZVEDP-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 5
- 229960002743 glutamine Drugs 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- HACUQVIGSVHRDG-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-(4-morpholin-4-ylanilino)triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NC(C=C1)=CC=C1N1CCOCC1 HACUQVIGSVHRDG-UHFFFAOYSA-N 0.000 description 4
- FUMWVJMVSTVBNU-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[(4-morpholin-4-ylphenyl)methylamino]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NCC(C=C1)=CC=C1N1CCOCC1 FUMWVJMVSTVBNU-UHFFFAOYSA-N 0.000 description 4
- HNNUBQWDWJNURV-UHFFFAOYSA-N 2-bromoethynyl-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)C#CBr HNNUBQWDWJNURV-UHFFFAOYSA-N 0.000 description 4
- XOSSGUMZKOBKKC-UHFFFAOYSA-N 4-[5-[(4-morpholin-4-ylphenyl)methylamino]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NCC=2C=CC(=CC=2)N2CCOCC2)=C1O XOSSGUMZKOBKKC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229930182566 Gentamicin Natural products 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 108010006519 Molecular Chaperones Proteins 0.000 description 4
- 102000005431 Molecular Chaperones Human genes 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- ONRHLGFTMJMBLV-UHFFFAOYSA-N ethynyl-(4-morpholin-4-ylphenyl)carbamic acid Chemical compound C(#C)N(C(O)=O)C1=CC=C(C=C1)N1CCOCC1 ONRHLGFTMJMBLV-UHFFFAOYSA-N 0.000 description 4
- 238000002875 fluorescence polarization Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000004172 nitrogen cycle Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- XHSBXSLFXCGQQD-DEOSSOPVSA-N (2s)-2-[[1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carbonyl]amino]-3-methylbutanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCOCC1 XHSBXSLFXCGQQD-DEOSSOPVSA-N 0.000 description 3
- MWTUOSWPJOUADP-XDJHFCHBSA-N (5z)-5-(4-hydroxy-6-oxo-3-propan-2-ylcyclohexa-2,4-dien-1-ylidene)-4-(1-methylindol-5-yl)-1,2,4-triazolidin-3-one Chemical compound O=C1C=C(O)C(C(C)C)=C\C1=C\1N(C=2C=C3C=CN(C)C3=CC=2)C(=O)NN/1 MWTUOSWPJOUADP-XDJHFCHBSA-N 0.000 description 3
- CKHCXYIYTCETLS-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCOCC1 CKHCXYIYTCETLS-UHFFFAOYSA-N 0.000 description 3
- AFFBHILSDHZADI-UHFFFAOYSA-N 1-nitro-2,4-bis(phenylmethoxy)-5-propan-2-ylbenzene Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC([N+]([O-])=O)=C1OCC1=CC=CC=C1 AFFBHILSDHZADI-UHFFFAOYSA-N 0.000 description 3
- PABSDEBPYZCAJX-UHFFFAOYSA-N 2,4-bis(phenylmethoxy)-5-propan-2-ylaniline Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC(N)=C1OCC1=CC=CC=C1 PABSDEBPYZCAJX-UHFFFAOYSA-N 0.000 description 3
- XESZOTRUYLRIEB-UHFFFAOYSA-N 4-[[4-[3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]phenyl]methyl]morpholine Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1OCC1=CC=CC=C1 XESZOTRUYLRIEB-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NZASFKUMGOJRED-UHFFFAOYSA-N [4-[3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]phenyl]methanol Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CO)=CC=2)=C1OCC1=CC=CC=C1 NZASFKUMGOJRED-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- QCZORVSTESPHCO-UHFFFAOYSA-N (4-ethynylphenyl)methanol Chemical compound OCC1=CC=C(C#C)C=C1 QCZORVSTESPHCO-UHFFFAOYSA-N 0.000 description 2
- MUUFMBNGPGHKDV-UHFFFAOYSA-N (4-morpholin-4-ylphenyl)methyl-[2-tri(propan-2-yl)silylethynyl]carbamic acid Chemical compound N1(CCOCC1)C1=CC=C(CN(C(O)=O)C#C[Si](C(C)C)(C(C)C)C(C)C)C=C1 MUUFMBNGPGHKDV-UHFFFAOYSA-N 0.000 description 2
- WRGVSXGTBXDVQW-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-[[4-(dimethylamino)piperidin-1-yl]methyl]phenyl]-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCC(N(C)C)CC1 WRGVSXGTBXDVQW-UHFFFAOYSA-N 0.000 description 2
- QRBBIONEOYUOBA-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-(piperazin-1-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCNCC1 QRBBIONEOYUOBA-UHFFFAOYSA-N 0.000 description 2
- VMXCKZIFERGZDF-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-(piperidin-1-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCCCC1 VMXCKZIFERGZDF-UHFFFAOYSA-N 0.000 description 2
- DBQMQBFEXOYJOS-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-[(2-morpholin-4-ylethylamino)methyl]phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CNCCN1CCOCC1 DBQMQBFEXOYJOS-UHFFFAOYSA-N 0.000 description 2
- PMFMGZJFZPEYMR-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCN(C)CC1 PMFMGZJFZPEYMR-UHFFFAOYSA-N 0.000 description 2
- QIWVPINCEFIBLF-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[4-[[ethyl(2-hydroxyethyl)amino]methyl]phenyl]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C1=CC=C(CN(CC)CCO)C=C1 QIWVPINCEFIBLF-UHFFFAOYSA-N 0.000 description 2
- XHCZHTWVOFCPRX-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-hexyl-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCCCCCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN1CCOCC1 XHCZHTWVOFCPRX-UHFFFAOYSA-N 0.000 description 2
- WYERJVSOFQIJJR-UHFFFAOYSA-N 1-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-N-hexyl-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound CCCCCCNC(=O)c1nnn(c1-c1ccc(CN2CCOCC2)cc1)-c1cc(C(C)C)c(OCc2ccccc2)cc1OCc1ccccc1 WYERJVSOFQIJJR-UHFFFAOYSA-N 0.000 description 2
- HDYDNYXXJBDDHO-UHFFFAOYSA-N 1-[[4-[3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]phenyl]methyl]piperidin-3-ol Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CC(O)CCC3)=CC=2)=C1OCC1=CC=CC=C1 HDYDNYXXJBDDHO-UHFFFAOYSA-N 0.000 description 2
- QETISTDEYMGRCN-UHFFFAOYSA-N 4-[5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1O QETISTDEYMGRCN-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- AIMKFQOZDDCIAX-UHFFFAOYSA-N 5-[4-(diethylaminomethyl)phenyl]-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C1=CC=C(CN(CC)CC)C=C1 AIMKFQOZDDCIAX-UHFFFAOYSA-N 0.000 description 2
- GSHAEQBERDNVBH-UHFFFAOYSA-N 5-[4-[(cyclohexylamino)methyl]phenyl]-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CNC1CCCCC1 GSHAEQBERDNVBH-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
- 206010063094 Cerebral malaria Diseases 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101710113864 Heat shock protein 90 Proteins 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- DKGJFBKYLFXAAJ-GSGGJQAMSA-N [(4E,8S,9S,10E,12S,13R,14S,16Z)-13,20,22-trihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,16,18(22),19-heptaen-9-yl] carbamate Chemical compound CO[C@H]1C\C(C)=C/c2c(O)c(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)cc(O)c2OC DKGJFBKYLFXAAJ-GSGGJQAMSA-N 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- RZBNLQYHQDCVPC-UHFFFAOYSA-N ethynyl-[(4-morpholin-4-ylphenyl)methyl]carbamic acid Chemical compound C1=CC(CN(C(=O)O)C#C)=CC=C1N1CCOCC1 RZBNLQYHQDCVPC-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229950004161 ganetespib Drugs 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- YCHKSCUYFXFORP-UHFFFAOYSA-N methyl 1-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-5-[4-(hydroxymethyl)phenyl]triazole-4-carboxylate Chemical compound COC(=O)C=1N=NN(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)C=1C1=CC=C(CO)C=C1 YCHKSCUYFXFORP-UHFFFAOYSA-N 0.000 description 2
- NQTDWHHEUQCSOW-UHFFFAOYSA-N methyl 1-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-5-[4-[[2-(diethylamino)ethylamino]methyl]phenyl]triazole-4-carboxylate Chemical compound C1=CC(CNCCN(CC)CC)=CC=C1C1=C(C(=O)OC)N=NN1C(C(=C1)OCC=2C=CC=CC=2)=CC(C(C)C)=C1OCC1=CC=CC=C1 NQTDWHHEUQCSOW-UHFFFAOYSA-N 0.000 description 2
- VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 2
- NCZKFFVXUCMMPH-UHFFFAOYSA-N n-cyclopentyl-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=C(C(=O)NC3CCCC3)N=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1O NCZKFFVXUCMMPH-UHFFFAOYSA-N 0.000 description 2
- VTJBQJOBKLNCDW-UHFFFAOYSA-N n-ethyl-2h-triazole-4-carboxamide Chemical compound CCNC(=O)C=1C=NNN=1 VTJBQJOBKLNCDW-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
- AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 2
- 229930192524 radicicol Natural products 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 2
- LBUZJDFCYIKEJK-UHFFFAOYSA-N tert-butyl N-[3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]-N-[(4-morpholin-4-ylphenyl)methyl]carbamate Chemical compound CC(C)c1cc(c(OCc2ccccc2)cc1OCc1ccccc1)-n1nncc1N(Cc1ccc(cc1)N1CCOCC1)C(=O)OC(C)(C)C LBUZJDFCYIKEJK-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 235000014393 valine Nutrition 0.000 description 2
- 229960004295 valine Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- FUJTWLNBGGBLPJ-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-5-[[4-(morpholin-4-ylmethyl)benzoyl]amino]triazole-4-carboxamide Chemical compound CCNC(=O)c1nnn(c1NC(=O)c1ccc(CN2CCOCC2)cc1)-c1cc(C(C)C)c(O)cc1O FUJTWLNBGGBLPJ-UHFFFAOYSA-N 0.000 description 1
- GKLXGLFKBOUBPK-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[(4-morpholin-4-ylbenzoyl)amino]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NC(=O)C(C=C1)=CC=C1N1CCOCC1 GKLXGLFKBOUBPK-UHFFFAOYSA-N 0.000 description 1
- CZOUDHZUZWUMJW-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[(4-piperidin-1-ylbenzoyl)amino]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NC(=O)C(C=C1)=CC=C1N1CCCCC1 CZOUDHZUZWUMJW-UHFFFAOYSA-N 0.000 description 1
- MFYWKUOGYVQFJM-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[[4-(3-hydroxypiperidin-1-yl)benzoyl]amino]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NC(=O)C(C=C1)=CC=C1N1CCCC(O)C1 MFYWKUOGYVQFJM-UHFFFAOYSA-N 0.000 description 1
- NCOGBAPNIBYJGP-UHFFFAOYSA-N 1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyl-5-[[4-(morpholin-4-ylmethyl)cyclohexanecarbonyl]amino]triazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1NC(=O)C(CC1)CCC1CN1CCOCC1 NCOGBAPNIBYJGP-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- QXSWHQGIEKUBAS-UHFFFAOYSA-N 1-ethynyl-4-fluorobenzene Chemical compound FC1=CC=C(C#C)C=C1 QXSWHQGIEKUBAS-UHFFFAOYSA-N 0.000 description 1
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- VHRXVQAJXHNNHS-UHFFFAOYSA-N 2,4-bis(phenylmethoxy)-1-propan-2-ylbenzene Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(C)C)=CC=C1OCC1=CC=CC=C1 VHRXVQAJXHNNHS-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- YAKSCLIHWCEFNU-UHFFFAOYSA-N 4-[5-[4-(1,2-oxazolidin-2-ylmethyl)phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound CC(C)c1cc(c(O)cc1O)-n1nncc1-c1ccc(CN2CCCO2)cc1 YAKSCLIHWCEFNU-UHFFFAOYSA-N 0.000 description 1
- USQXESLZFNXZQP-UHFFFAOYSA-N 4-[5-[4-(piperidin-1-ylmethyl)phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCCCC3)=CC=2)=C1O USQXESLZFNXZQP-UHFFFAOYSA-N 0.000 description 1
- MKBBWHFACZDCOH-UHFFFAOYSA-N 4-[5-[4-[(4-phenylpiperazin-1-yl)methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3CCN(CC3)C=3C=CC=CC=3)=CC=2)=C1O MKBBWHFACZDCOH-UHFFFAOYSA-N 0.000 description 1
- DEYGCWDOMSNVOT-UHFFFAOYSA-N 4-[5-[4-[[2-(2-hydroxyethyl)piperidin-1-yl]methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)C=2C=CC(CN3C(CCCC3)CCO)=CC=2)=C1O DEYGCWDOMSNVOT-UHFFFAOYSA-N 0.000 description 1
- JOXXZWQGNIULBA-UHFFFAOYSA-N 4-[5-[4-[[ethyl(2-hydroxyethyl)amino]methyl]phenyl]triazol-1-yl]-6-propan-2-ylbenzene-1,3-diol Chemical compound C1=CC(CN(CCO)CC)=CC=C1C1=CN=NN1C1=CC(C(C)C)=C(O)C=C1O JOXXZWQGNIULBA-UHFFFAOYSA-N 0.000 description 1
- JQVAPEJNIZULEK-UHFFFAOYSA-N 4-chlorobenzene-1,3-diol Chemical compound OC1=CC=C(Cl)C(O)=C1 JQVAPEJNIZULEK-UHFFFAOYSA-N 0.000 description 1
- KGAKOACEBMLXIK-UHFFFAOYSA-N 5-[4-[(4-benzylpiperazin-1-yl)methyl]phenyl]-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C(C=C1)=CC=C1CN(CC1)CCN1CC1=CC=CC=C1 KGAKOACEBMLXIK-UHFFFAOYSA-N 0.000 description 1
- OJKALDMOCOACDI-UHFFFAOYSA-N 5-[4-[[3-(diethylamino)propylamino]methyl]phenyl]-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-n-ethyltriazole-4-carboxamide Chemical compound CCNC(=O)C=1N=NN(C=2C(=CC(O)=C(C(C)C)C=2)O)C=1C1=CC=C(CNCCCN(CC)CC)C=C1 OJKALDMOCOACDI-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 102100032187 Androgen receptor Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- QULDDKSCVCJTPV-UHFFFAOYSA-N BIIB021 Chemical compound COC1=C(C)C=NC(CN2C3=NC(N)=NC(Cl)=C3N=C2)=C1C QULDDKSCVCJTPV-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- RVAQIUULWULRNW-UHFFFAOYSA-N Ganetespib Chemical compound C1=C(O)C(C(C)C)=CC(C=2N(C(O)=NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O RVAQIUULWULRNW-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000010726 Glycine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010063380 Glycine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- GSUOVFJJGRKABZ-UHFFFAOYSA-N [1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-4-yl]-morpholin-4-ylmethanone Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=C(C(=O)N3CCOCC3)N=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1O GSUOVFJJGRKABZ-UHFFFAOYSA-N 0.000 description 1
- JCXKKHHVQGQABE-UHFFFAOYSA-N [3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-(4-morpholin-4-ylphenyl)carbamic acid Chemical compound OC1=C(C=C(C(=C1)O)C(C)C)N1N=NC=C1N(C(O)=O)C1=CC=C(C=C1)N1CCOCC1 JCXKKHHVQGQABE-UHFFFAOYSA-N 0.000 description 1
- VLUCXEUKDZZGBQ-UHFFFAOYSA-N [3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]-(4-morpholin-4-ylphenyl)carbamic acid Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C(=C1)OCC1=CC=CC=C1)C(C)C)N1N=NC=C1N(C(O)=O)C1=CC=C(C=C1)N1CCOCC1 VLUCXEUKDZZGBQ-UHFFFAOYSA-N 0.000 description 1
- IUBQORRUGVCRHX-UHFFFAOYSA-N [3-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]triazol-4-yl]-[(4-morpholin-4-ylphenyl)methyl]carbamic acid Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C(=C1)OCC1=CC=CC=C1)C(C)C)N1N=NC=C1N(C(O)=O)CC1=CC=C(C=C1)N1CCOCC1 IUBQORRUGVCRHX-UHFFFAOYSA-N 0.000 description 1
- JNWFIPVDEINBAI-UHFFFAOYSA-N [5-hydroxy-4-[4-(1-methylindol-5-yl)-5-oxo-1H-1,2,4-triazol-3-yl]-2-propan-2-ylphenyl] dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C(C(C)C)=CC(C=2N(C(=O)NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O JNWFIPVDEINBAI-UHFFFAOYSA-N 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000007080 aromatic substitution reaction Methods 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000008316 benzisoxazoles Chemical class 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- VCIZMGNKKFEEHA-UHFFFAOYSA-N chembl1082237 Chemical group C=1C=C2C(NC(=O)CCC)=NNC2=CC=1C1=CC=C(O)C=C1 VCIZMGNKKFEEHA-UHFFFAOYSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- HTRTVURHRBFPFA-UHFFFAOYSA-N ethyl 1-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxylate Chemical compound CCOC(=O)c1nnn(c1-c1ccc(CN2CCOCC2)cc1)-c1cc(C(C)C)c(OCc2ccccc2)cc1OCc1ccccc1 HTRTVURHRBFPFA-UHFFFAOYSA-N 0.000 description 1
- APRILKFBGZRBKC-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)prop-2-ynoate Chemical compound CCOC(=O)C#CC1=CC=C(F)C=C1 APRILKFBGZRBKC-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- KZGWPHUWNWRTEP-UHFFFAOYSA-N ethynyl-tri(propan-2-yl)silane Chemical group CC(C)[Si](C#C)(C(C)C)C(C)C KZGWPHUWNWRTEP-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 0.000 description 1
- 235000014705 isoleucine Nutrition 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- OUPHLNHIDPKHJF-UHFFFAOYSA-N methyl 1-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxylate Chemical compound COC(=O)c1nnn(c1-c1ccc(CN2CCOCC2)cc1)-c1cc(C(C)C)c(OCc2ccccc2)cc1OCc1ccccc1 OUPHLNHIDPKHJF-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- CJFMDQHCWOVQSO-UHFFFAOYSA-N n-(2-chloroethyl)-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=C(C(=O)NCCCl)N=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1O CJFMDQHCWOVQSO-UHFFFAOYSA-N 0.000 description 1
- ACJSGTGRAKYUQY-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-(3-hydroxypiperidin-1-yl)benzamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C=2C=CC(=CC=2)N2CC(O)CCC2)=C1O ACJSGTGRAKYUQY-UHFFFAOYSA-N 0.000 description 1
- YGLOTNFZFCMVRU-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-(morpholin-4-ylmethyl)benzamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C=2C=CC(CN3CCOCC3)=CC=2)=C1O YGLOTNFZFCMVRU-UHFFFAOYSA-N 0.000 description 1
- FQJVHYHXQNUAOG-UHFFFAOYSA-N n-[3-(2,4-dihydroxy-5-propan-2-ylphenyl)triazol-4-yl]-4-pyrrolidin-1-ylbenzamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=CN=N2)NC(=O)C=2C=CC(=CC=2)N2CCCC2)=C1O FQJVHYHXQNUAOG-UHFFFAOYSA-N 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- DKKADLLUEKFSFF-UHFFFAOYSA-N n-cyclohexyl-1-(2,4-dihydroxy-5-propan-2-ylphenyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazole-4-carboxamide Chemical compound C1=C(O)C(C(C)C)=CC(N2C(=C(C(=O)NC3CCCCC3)N=N2)C=2C=CC(CN3CCOCC3)=CC=2)=C1O DKKADLLUEKFSFF-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 235000008729 phenylalanine Nutrition 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920001184 polypeptide 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
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000004400 serine Nutrition 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229950007866 tanespimycin Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GLSCJMOXSXLLCP-UHFFFAOYSA-N tert-butyl n-ethynyl-n-(4-morpholin-4-ylphenyl)carbamate Chemical compound C1=CC(N(C#C)C(=O)OC(C)(C)C)=CC=C1N1CCOCC1 GLSCJMOXSXLLCP-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 239000003856 thrombin receptor antagonist Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
- 230000002034 xenobiotic effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- 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
-
- 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
- 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
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- 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
- 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
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
- C07D403/10—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 linked by a carbon chain containing aromatic rings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Immunology (AREA)
- Psychology (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10195949 | 2010-12-20 | ||
| PCT/EP2011/072558 WO2012084602A1 (en) | 2010-12-20 | 2011-12-13 | Aryl triazole compounds with antitumoural activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2655345T3 true DK2655345T3 (en) | 2015-05-04 |
Family
ID=43901588
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK11805449.3T DK2655345T3 (en) | 2010-12-20 | 2011-12-13 | Aryltriazole Compounds with Anti-tumor Effect |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9302998B2 (enExample) |
| EP (1) | EP2655345B1 (enExample) |
| JP (1) | JP2014501232A (enExample) |
| AR (1) | AR084361A1 (enExample) |
| CY (1) | CY1116297T1 (enExample) |
| DK (1) | DK2655345T3 (enExample) |
| ES (1) | ES2536980T3 (enExample) |
| HR (1) | HRP20150450T1 (enExample) |
| HU (1) | HUE025697T2 (enExample) |
| ME (1) | ME02144B (enExample) |
| PL (1) | PL2655345T3 (enExample) |
| PT (1) | PT2655345E (enExample) |
| RS (1) | RS53966B1 (enExample) |
| SI (1) | SI2655345T1 (enExample) |
| SM (1) | SMT201500115B (enExample) |
| WO (1) | WO2012084602A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101676208B1 (ko) * | 2012-09-17 | 2016-11-14 | 에프. 호프만-라 로슈 아게 | 트라이아졸 카복스아미드 유도체 |
| CN103275023B (zh) * | 2013-06-08 | 2015-10-07 | 浙江工业大学 | 1-芳基-1,2,3-三氮唑类化合物及其制备和应用 |
| CN107540624B (zh) * | 2016-06-29 | 2020-06-16 | 广州市恒诺康医药科技有限公司 | 热休克蛋白抑制剂及其制备方法和应用 |
| WO2018081814A1 (en) * | 2016-10-31 | 2018-05-03 | University Of Kansas | Grp94 selective inhibitors and uses thereof |
| WO2019040869A1 (en) * | 2017-08-25 | 2019-02-28 | The Trustees Of Columbia University In The City Of New York | INHIBITORS OF IMPORTS OF PURINE IN PARASITES AND USES OF THESE INHIBITORS |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| CN110590686B (zh) * | 2019-10-31 | 2022-10-25 | 重庆大学 | 一种氮杂糖基1,2,3-三氮唑核苷化合物及其制备方法和应用 |
| WO2021137665A1 (ko) * | 2019-12-30 | 2021-07-08 | 이화여자대학교 산학협력단 | Hsp90 억제제로서의 1,2,3-트리아졸 유도체 화합물 및 이의 용도 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10315570A1 (de) | 2003-04-05 | 2004-10-14 | Merck Patent Gmbh | Triazolderivate |
| GB0315111D0 (en) | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| GB0323810D0 (en) | 2003-10-10 | 2003-11-12 | Cancer Rec Tech Ltd | Pyridothiophene compounds |
| ES2594874T3 (es) | 2004-11-18 | 2016-12-23 | Synta Pharmaceuticals Corp. | Compuestos de triazol que modulan la actividad de HSP90 |
| WO2006109846A1 (ja) | 2005-04-06 | 2006-10-19 | Takeda Pharmaceutical Company Limited | トリアゾール誘導体およびその用途 |
| JP2006306755A (ja) * | 2005-04-27 | 2006-11-09 | Nippon Kayaku Co Ltd | 新規なピラゾール誘導体とそれを有効成分とするｈｓｐ９０阻害剤 |
| JP5149177B2 (ja) * | 2005-07-25 | 2013-02-20 | シンタ ファーマシューティカルズ コーポレーション | 増殖性疾患の治療のための、チューブリンポリマー化の１，２，３−トリアゾール系抑制剤 |
| CA2664852A1 (en) * | 2006-10-03 | 2008-04-10 | Nippon Kayaku Kabushiki Kaisha | High-molecular weight conjugate of resorcinol derivatives |
| NZ579403A (en) * | 2007-02-08 | 2012-03-30 | Synta Pharmaceuticals Corp | Triazole compounds that are useful in the treatment of proliferative disorders, such as cancer |
| WO2009115486A1 (en) | 2008-03-18 | 2009-09-24 | Glaxo Group Limited | Triazole amide derivatives for use in therapy |
| LT5623B (lt) | 2008-04-30 | 2010-01-25 | Biotechnologijos Institutas, , | 5-aril-4-(5-pakeistieji 2,4-dihidroksifenil)-1,2,3-tiadiazolai kaip hsp90 šaperono slopikliai ir tarpiniai junginiai jiems gauti |
| WO2009139916A1 (en) | 2008-05-16 | 2009-11-19 | Synta Pharmaceuticals Corp. | Tricyclic triazole compounds that modulate hsp90 activity |
| US9126953B2 (en) | 2008-08-08 | 2015-09-08 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate HSP90 activity |
| EP2323737A2 (en) | 2008-08-08 | 2011-05-25 | Synta Pharmaceuticals Corp. | Triazole compounds that modulate hsp90 activity |
-
2011
- 2011-12-13 ME MEP-2015-62A patent/ME02144B/me unknown
- 2011-12-13 HU HUE11805449A patent/HUE025697T2/en unknown
- 2011-12-13 RS RS20150294A patent/RS53966B1/sr unknown
- 2011-12-13 EP EP11805449.3A patent/EP2655345B1/en active Active
- 2011-12-13 WO PCT/EP2011/072558 patent/WO2012084602A1/en not_active Ceased
- 2011-12-13 PT PT118054493T patent/PT2655345E/pt unknown
- 2011-12-13 SI SI201130488T patent/SI2655345T1/sl unknown
- 2011-12-13 JP JP2013543700A patent/JP2014501232A/ja active Pending
- 2011-12-13 ES ES11805449.3T patent/ES2536980T3/es active Active
- 2011-12-13 PL PL11805449T patent/PL2655345T3/pl unknown
- 2011-12-13 US US13/996,359 patent/US9302998B2/en not_active Expired - Fee Related
- 2011-12-13 HR HRP20150450TT patent/HRP20150450T1/hr unknown
- 2011-12-13 DK DK11805449.3T patent/DK2655345T3/en active
- 2011-12-19 AR ARP110104771A patent/AR084361A1/es not_active Application Discontinuation
-
2015
- 2015-05-15 SM SM201500115T patent/SMT201500115B/xx unknown
- 2015-05-15 CY CY20151100441T patent/CY1116297T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL2655345T3 (pl) | 2015-07-31 |
| EP2655345A1 (en) | 2013-10-30 |
| SMT201500115B (it) | 2015-07-09 |
| US9302998B2 (en) | 2016-04-05 |
| RS53966B1 (sr) | 2015-08-31 |
| WO2012084602A1 (en) | 2012-06-28 |
| ME02144B (me) | 2015-10-20 |
| EP2655345B1 (en) | 2015-02-18 |
| AR084361A1 (es) | 2013-05-08 |
| HUE025697T2 (en) | 2016-04-28 |
| US20140329812A1 (en) | 2014-11-06 |
| PT2655345E (pt) | 2015-06-09 |
| ES2536980T3 (es) | 2015-06-01 |
| CY1116297T1 (el) | 2017-02-08 |
| JP2014501232A (ja) | 2014-01-20 |
| SI2655345T1 (sl) | 2015-06-30 |
| HRP20150450T1 (hr) | 2015-06-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9302998B2 (en) | Aryl triazole compounds with antitumoural activity | |
| EP2310377B1 (en) | 5-phenyl-isoxazole-3-carboxamides modulating hsp90 with antitumoral activities | |
| ES2375527T3 (es) | Derivados 1,2-disustituidos-4-bencilamino-pirrolidina como inhibidores cetp útiles para el tratamiento de enfermedades tales como hiperlipidemia o arteriosclerosis. | |
| JP6746614B2 (ja) | ウレア誘導体、またはその薬理学的に許容される塩 | |
| AU2017266325B2 (en) | Imidazoles as histone demethylase inhibitors | |
| BR122014026114A2 (pt) | Compostos de fórmula (i), composição farmacêutica e uso do composto | |
| EA010132B1 (ru) | Производные триазола в качестве антагонистов вазопрессина | |
| CA3248726A1 (en) | Kinesin 18A-type protein inhibitor and its use | |
| CA2907528A1 (en) | Novel compounds | |
| JP6877771B2 (ja) | ピロリジン誘導体 | |
| NO333800B1 (no) | Arylamidin-derivat eller salt derav samt antisoppmiddel inneholdende samme | |
| KR20180083411A (ko) | 1,3,4-티아디아졸 화합물 및 암 치료시 이의 용도 | |
| AU2016363719B2 (en) | 1,3,4-thiadiazole compounds and their use in treating cancer | |
| WO2022150316A1 (en) | C-myc mrna translation modulators and uses thereof in the treatment of cancer | |
| WO2012099200A1 (ja) | ピラゾール誘導体 | |
| CA3071235A1 (en) | Therapeutic agent or preventive agent for alopecia areata | |
| CA2999940A1 (en) | Substituted morpholine derivatives having activity against pain | |
| TW201249814A (en) | Aryl triazole compounds with antitumoural activity | |
| WO2026104812A1 (en) | Rab27 inhibitors | |
| WO2024133292A1 (en) | Novel ccr8 antagonists | |
| HK1158191A (en) | 5-phenyl-isoxazole-3-carboxamides modulating hsp90 with antitumoral activities | |
| BR112017002053B1 (pt) | Composto de acordo com a fórmula (xi) e uso de um composto | |
| BR122023020299A2 (pt) | Composto, uso de um composto, composição farmacêutica e processo para preparação de um composto |