TWI693220B - １,３,４-噻二唑化合物及其用於治療癌症之用途 - Google Patents
１,３,４-噻二唑化合物及其用於治療癌症之用途 Download PDFInfo
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- TWI693220B TWI693220B TW104117531A TW104117531A TWI693220B TW I693220 B TWI693220 B TW I693220B TW 104117531 A TW104117531 A TW 104117531A TW 104117531 A TW104117531 A TW 104117531A TW I693220 B TWI693220 B TW I693220B
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- Prior art keywords
- acetamide
- amino
- methoxy
- thiadiazol
- phenyl
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 98
- 201000011510 cancer Diseases 0.000 title claims abstract description 83
- 150000004869 1,3,4-thiadiazoles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 237
- 150000003839 salts Chemical class 0.000 claims abstract description 215
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 36
- 201000010099 disease Diseases 0.000 claims abstract description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 230000001404 mediated effect Effects 0.000 claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 102100025960 Glutaminase kidney isoform, mitochondrial Human genes 0.000 claims abstract 6
- 101000856990 Homo sapiens Glutaminase kidney isoform, mitochondrial Proteins 0.000 claims abstract 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 259
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 131
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 58
- -1 1,2,4-triazin-3-yl Chemical group 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 239000003814 drug Substances 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 239000003085 diluting agent Substances 0.000 claims description 19
- 150000002431 hydrogen Chemical group 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 238000002560 therapeutic procedure Methods 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 239000011737 fluorine Chemical group 0.000 claims description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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| GB201520959D0 (en) | 2015-11-27 | 2016-01-13 | Astrazeneca Ab And Cancer Res Technology Ltd | Bis-pyridazine compounds and their use in treating cancer |
| US9938265B2 (en) * | 2015-11-30 | 2018-04-10 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
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| EP2922832B1 (en) | 2012-11-21 | 2019-10-09 | Agios Pharmaceuticals, Inc. | Glutaminase inhibitors and methods of use |
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| WO2014079011A1 (en) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Heterocyclic compounds for inhibiting glutaminase and their methods of use |
| CA2892817A1 (en) | 2012-12-03 | 2014-06-12 | Calithera Biosciences Inc. | Treatment of cancer with heterocyclic inhibitors of glutaminase |
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