ES2796562T3 - Compuestos de 1,3,4-tiadiazol y su uso en el tratamiento del cáncer - Google Patents
Compuestos de 1,3,4-tiadiazol y su uso en el tratamiento del cáncer Download PDFInfo
- Publication number
- ES2796562T3 ES2796562T3 ES16805078T ES16805078T ES2796562T3 ES 2796562 T3 ES2796562 T3 ES 2796562T3 ES 16805078 T ES16805078 T ES 16805078T ES 16805078 T ES16805078 T ES 16805078T ES 2796562 T3 ES2796562 T3 ES 2796562T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- thiadiazol
- acetamide
- ylpyrrolidin
- pyridazin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 206010028980 Neoplasm Diseases 0.000 title claims description 44
- 201000011510 cancer Diseases 0.000 title claims description 40
- 238000011282 treatment Methods 0.000 title claims description 19
- 150000004869 1,3,4-thiadiazoles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 150000003839 salts Chemical class 0.000 claims abstract description 103
- -1 6-fluoropyridazin-3-yl Chemical group 0.000 claims abstract description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 26
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims abstract description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 19
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- DFZKJNIPSCUEPU-WBVHZDCISA-N (2S)-2-(dimethylamino)-2-phenyl-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound CN([C@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC=CC=1)C1=CC=CC=C1)C DFZKJNIPSCUEPU-WBVHZDCISA-N 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 206010038389 Renal cancer Diseases 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- 201000010982 kidney cancer Diseases 0.000 claims description 5
- 208000014018 liver neoplasm Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- RYLPEZCPWSMRJX-AEFFLSMTSA-N (2S)-2-(3-cyanophenyl)-2-(dimethylamino)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound CN(C)[C@H](C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1)C1=CC(=CC=C1)C#N RYLPEZCPWSMRJX-AEFFLSMTSA-N 0.000 claims description 4
- BGDBGDSBJNRQII-KDOFPFPSSA-N (2S)-2-(azetidin-1-yl)-2-[4-fluoro-3-(trifluoromethoxy)phenyl]-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC1=C(OC(F)(F)F)C=C(C=C1)[C@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 BGDBGDSBJNRQII-KDOFPFPSSA-N 0.000 claims description 4
- WTQONOHFHMAUDR-KDOFPFPSSA-N (2S)-2-(azetidin-1-yl)-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide Chemical compound FC1=CC=C(N=N1)N1CC[C@H](C1)NC1=NN=C(NC(=O)[C@@H](N2CCC2)C2=CC(OC(F)(F)F)=CC=C2)S1 WTQONOHFHMAUDR-KDOFPFPSSA-N 0.000 claims description 4
- UKMGKJMWJSTMMW-QAPCUYQASA-N (2S)-2-(azetidin-1-yl)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide Chemical compound FC(F)(F)OC1=CC=CC(=C1)[C@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 UKMGKJMWJSTMMW-QAPCUYQASA-N 0.000 claims description 4
- ZLUNIMIQWCCCHH-WBVHZDCISA-N (2S)-2-(dimethylamino)-2-(4-fluorophenyl)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound CN(C)[C@H](C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1)C1=CC=C(F)C=C1 ZLUNIMIQWCCCHH-WBVHZDCISA-N 0.000 claims description 4
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- ACKNLXUAODVKMJ-CRAIPNDOSA-N (1R)-2-methyl-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-3,4-dihydro-1H-isoquinoline-1-carboxamide Chemical compound CN1CCC2=C(C=CC=C2)[C@@H]1C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 ACKNLXUAODVKMJ-CRAIPNDOSA-N 0.000 claims description 3
- VOPBRZXKPSPMAY-APWZRJJASA-N (2S)-2-(azetidin-1-yl)-2-(3-methoxyphenyl)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound COC1=CC=CC(=C1)[C@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 VOPBRZXKPSPMAY-APWZRJJASA-N 0.000 claims description 3
- JGRRPMNEWJNJGZ-QAPCUYQASA-N (2S)-2-(azetidin-1-yl)-2-[3-(difluoromethoxy)phenyl]-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC(F)OC1=CC=CC(=C1)[C@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 JGRRPMNEWJNJGZ-QAPCUYQASA-N 0.000 claims description 3
- NBPVIHVBADJLHI-PBHICJAKSA-N (2S)-2-(dimethylamino)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide Chemical compound CN([C@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC=CC=1)C1=CC(=CC=C1)OC(F)(F)F)C NBPVIHVBADJLHI-PBHICJAKSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- VOPBRZXKPSPMAY-VQIMIIECSA-N (2R)-2-(azetidin-1-yl)-2-(3-methoxyphenyl)-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound COC1=CC=CC(=C1)[C@@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 VOPBRZXKPSPMAY-VQIMIIECSA-N 0.000 claims description 2
- BGDBGDSBJNRQII-RDTXWAMCSA-N (2R)-2-(azetidin-1-yl)-2-[4-fluoro-3-(trifluoromethoxy)phenyl]-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC1=C(OC(F)(F)F)C=C(C=C1)[C@@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 BGDBGDSBJNRQII-RDTXWAMCSA-N 0.000 claims description 2
- DFZKJNIPSCUEPU-NVXWUHKLSA-N (2R)-2-(dimethylamino)-2-phenyl-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound CN(C)[C@@H](C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1)C1=CC=CC=C1 DFZKJNIPSCUEPU-NVXWUHKLSA-N 0.000 claims description 2
- JGRRPMNEWJNJGZ-CRAIPNDOSA-N (2R)-2-(azetidin-1-yl)-2-[3-(difluoromethoxy)phenyl]-N-[5-[[(3R)-1-pyridazin-3-ylpyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC(F)OC1=CC=CC(=C1)[C@@H](N1CCC1)C(=O)NC1=NN=C(N[C@@H]2CCN(C2)C2=CC=CN=N2)S1 JGRRPMNEWJNJGZ-CRAIPNDOSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
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- 239000011737 fluorine Substances 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 103
- 239000000243 solution Substances 0.000 description 86
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 38
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 36
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
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| US9938265B2 (en) | 2015-11-30 | 2018-04-10 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| US10323028B2 (en) | 2015-11-30 | 2019-06-18 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| ES2939506T3 (es) | 2018-10-16 | 2023-04-24 | Medshine Discovery Inc | Derivado de tiadiazol y usos del mismo como inhibidor de GLS1 para el tratamiento de cáncer |
| CN114560855B (zh) * | 2021-03-26 | 2023-05-23 | 成都苑东生物制药股份有限公司 | 环烷基甲酰胺类衍生物、其制备方法及用途 |
| WO2025196447A1 (en) | 2024-03-22 | 2025-09-25 | Sitryx Therapeutics Limited | Thiadiazoles as glutaminase 1 inhibitors |
| WO2025196446A1 (en) | 2024-03-22 | 2025-09-25 | Sitryx Therapeutics Limited | Thiadiazoles as glutaminase 1 inhibitors |
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| CN108785305B (zh) * | 2011-11-21 | 2021-10-29 | 卡利泰拉生物科技公司 | 谷氨酰胺酶的杂环抑制剂 |
| WO2014079011A1 (en) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Heterocyclic compounds for inhibiting glutaminase and their methods of use |
| KR20160100407A (ko) | 2014-01-06 | 2016-08-23 | 리젠 파마슈티컬스 소시에떼 아노님 | 신규한 글루타미나제의 저해제 |
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