ES2759940T3 - Compuestos de 1,3,4-tiadiazol y su uso para tratar el cáncer - Google Patents
Compuestos de 1,3,4-tiadiazol y su uso para tratar el cáncer Download PDFInfo
- Publication number
- ES2759940T3 ES2759940T3 ES16802102T ES16802102T ES2759940T3 ES 2759940 T3 ES2759940 T3 ES 2759940T3 ES 16802102 T ES16802102 T ES 16802102T ES 16802102 T ES16802102 T ES 16802102T ES 2759940 T3 ES2759940 T3 ES 2759940T3
- Authority
- ES
- Spain
- Prior art keywords
- methoxy
- amino
- pyrrolidin
- thiadiazol
- acetamide
- 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 46
- 201000011510 cancer Diseases 0.000 title claims description 40
- 150000004869 1,3,4-thiadiazoles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 150000003839 salts Chemical class 0.000 claims abstract description 84
- -1 5-methylpyridazin-3-yl Chemical group 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 15
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 11
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 11
- 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
- FSLVAZAHHSXHCR-WBMJQRKESA-N (2S)-2-[3-(difluoromethoxy)phenyl]-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxyacetamide Chemical compound FC(OC=1C=C(C=CC=1)[C@@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC(=CC=1)F)OC)F FSLVAZAHHSXHCR-WBMJQRKESA-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
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 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
- 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- SKUZHMFUXHGQQW-DYVFJYSZSA-N (2S)-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-(3-methoxyphenyl)acetamide Chemical compound FC1=CC=C(N=N1)N1C[C@@H](CC1)NC1=NN=C(S1)NC([C@H](C1=CC(=CC=C1)OC)OC)=O SKUZHMFUXHGQQW-DYVFJYSZSA-N 0.000 claims description 3
- BILNGVPSJLOCKW-CJNGLKHVSA-N (2S)-N-[5-[[(3R)-1-(6-fluoropyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-methoxy-2-phenylacetamide Chemical compound FC1=CC=C(N=N1)N1C[C@@H](CC1)NC1=NN=C(S1)NC([C@H](C1=CC=CC=C1)OC)=O BILNGVPSJLOCKW-CJNGLKHVSA-N 0.000 claims description 3
- CQLPOXGXACFBIW-PBHICJAKSA-N (2S)-2-methoxy-N-[5-[[(3R)-1-(6-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide Chemical compound CO[C@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC(=CC=1)C)C1=CC(=CC=C1)OC(F)(F)F CQLPOXGXACFBIW-PBHICJAKSA-N 0.000 claims description 2
- HXFKMUYISOOFNN-WBVHZDCISA-N (2S)-2-(4-fluorophenyl)-2-methoxy-N-[5-[[(3R)-1-(6-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC1=CC=C(C=C1)[C@@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC(=CC=1)C)OC HXFKMUYISOOFNN-WBVHZDCISA-N 0.000 claims 2
- CJPDRLNNFXCJTE-QAPCUYQASA-N (2S)-2-methoxy-2-(3-methoxyphenyl)-N-[5-[[(3R)-1-(6-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound CO[C@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC(=CC=1)C)C1=CC(=CC=C1)OC CJPDRLNNFXCJTE-QAPCUYQASA-N 0.000 claims 2
- QFAHGXFMNKFWKL-KDOFPFPSSA-N (2S)-2-(4-fluoro-3-methoxyphenyl)-2-methoxy-N-[5-[[(3R)-1-(6-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC1=C(C=C(C=C1)[C@@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC(=CC=1)C)OC)OC QFAHGXFMNKFWKL-KDOFPFPSSA-N 0.000 claims 1
- NKPBNEQDGYAJFW-WBVHZDCISA-N (2S)-2-(4-fluorophenyl)-2-methoxy-N-[5-[[(3R)-1-(5-methylpyridazin-3-yl)pyrrolidin-3-yl]amino]-1,3,4-thiadiazol-2-yl]acetamide Chemical compound FC1=CC=C(C=C1)[C@@H](C(=O)NC=1SC(=NN=1)N[C@H]1CN(CC1)C=1N=NC=C(C=1)C)OC NKPBNEQDGYAJFW-WBVHZDCISA-N 0.000 claims 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 214
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- 239000000203 mixture Substances 0.000 description 44
- 239000000543 intermediate Substances 0.000 description 41
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 38
- 108010073324 Glutaminase Proteins 0.000 description 35
- 102000009127 Glutaminase Human genes 0.000 description 35
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 29
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 28
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- 239000000243 solution Substances 0.000 description 25
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- 239000000047 product Substances 0.000 description 22
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- 230000002829 reductive effect Effects 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 229910052681 coesite Inorganic materials 0.000 description 17
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
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- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 14
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
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- 210000004027 cell Anatomy 0.000 description 13
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 12
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- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 10
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
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| US201562260787P | 2015-11-30 | 2015-11-30 | |
| PCT/EP2016/079251 WO2017093300A1 (en) | 2015-11-30 | 2016-11-30 | 1,3,4-thiadiazole compounds and their use in treating cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2759940T3 true ES2759940T3 (es) | 2020-05-12 |
| ES2759940T8 ES2759940T8 (es) | 2020-05-20 |
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| ES16802102T Active ES2759940T3 (es) | 2015-11-30 | 2016-11-30 | Compuestos de 1,3,4-tiadiazol y su uso para tratar el cáncer |
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| SV (1) | SV2018005701A (enExample) |
| TN (1) | TN2018000126A1 (enExample) |
| TW (1) | TW201730188A (enExample) |
| WO (1) | WO2017093300A1 (enExample) |
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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 |
| TW201731511A (zh) * | 2015-11-30 | 2017-09-16 | 阿斯特捷利康公司 | １，３，４-噻二唑化合物及其在治療癌症中之用途 |
| 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 |
| WO2025196446A1 (en) * | 2024-03-22 | 2025-09-25 | Sitryx Therapeutics Limited | Thiadiazoles as glutaminase 1 inhibitors |
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| ES2295068T3 (es) * | 1999-11-24 | 2008-04-16 | MERCK & CO., INC. | Gamma-hidroxi-2-(fluoroalquilaminocarbonil)-1-piperazinpentanamidas como inhibidores de la proteasa del vih. |
| US6451828B1 (en) * | 2000-08-10 | 2002-09-17 | Elan Pharmaceuticals, Inc. | Selective inhibition of glutaminase by bis-thiadiazoles |
| AR044688A1 (es) * | 2003-06-12 | 2005-09-21 | Euro Celtique Sa | Agentes terapeuticos utiles para el tratamiento del dolor |
| WO2006053342A2 (en) * | 2004-11-12 | 2006-05-18 | Osi Pharmaceuticals, Inc. | Integrin antagonists useful as anticancer agents |
| MX2011011094A (es) * | 2009-04-20 | 2011-11-04 | Hoffmann La Roche | Derivados de prolina como inhibidores de catepsina. |
| 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 |
| HUE056078T2 (hu) * | 2012-11-16 | 2022-01-28 | Calithera Biosciences Inc | Heterociklusos glutamináz inhibitorok |
| 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 |
| WO2015138902A1 (en) * | 2014-03-14 | 2015-09-17 | Calithera Biosciences, Inc. | Combination therapy with glutaminase inhibitors |
| GB201409624D0 (en) | 2014-05-30 | 2014-07-16 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
| TW201731511A (zh) | 2015-11-30 | 2017-09-16 | 阿斯特捷利康公司 | １，３，４-噻二唑化合物及其在治療癌症中之用途 |
| US10323028B2 (en) | 2015-11-30 | 2019-06-18 | Astrazeneca Ab | 1,3,4-thiadiazole compounds and their use in treating cancer |
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2016
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- 2016-11-30 MX MX2018006528A patent/MX2018006528A/es unknown
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| MX2018006528A (es) | 2019-05-15 |
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| US9938265B2 (en) | 2018-04-10 |
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| SV2018005701A (es) | 2018-11-27 |
| AU2016363719A1 (en) | 2018-07-05 |
| DOP2018000134A (es) | 2018-06-30 |
| DK3383871T3 (da) | 2019-12-16 |
| AR106876A1 (es) | 2018-02-28 |
| JP2019501134A (ja) | 2019-01-17 |
| IL258644A (en) | 2018-06-28 |
| JP6873132B2 (ja) | 2021-05-19 |
| EP3383871A1 (en) | 2018-10-10 |
| CN108349967B (zh) | 2022-02-15 |
| AU2016363719A8 (en) | 2018-07-12 |
| TN2018000126A1 (en) | 2019-10-04 |
| CN108349967A (zh) | 2018-07-31 |
| KR20180083412A (ko) | 2018-07-20 |
| TW201730188A (zh) | 2017-09-01 |
| US20170152254A1 (en) | 2017-06-01 |
| EA201891240A1 (ru) | 2018-11-30 |
| PH12018501132A1 (en) | 2019-01-21 |
| ES2759940T8 (es) | 2020-05-20 |
| PE20181450A1 (es) | 2018-09-12 |
| AU2016363719B2 (en) | 2019-11-14 |
| CA3005516A1 (en) | 2017-06-08 |
| CA3005516C (en) | 2024-04-16 |
| CL2018001408A1 (es) | 2018-10-12 |
| BR112018010812A2 (pt) | 2018-11-27 |
| SG11201803813UA (en) | 2018-06-28 |
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