ES2656471T3 - Derivados de pirazolo-pirrolidin-4-ona como inhibidores de BET y su uso en el tratamiento de enfermedades - Google Patents
Derivados de pirazolo-pirrolidin-4-ona como inhibidores de BET y su uso en el tratamiento de enfermedades Download PDFInfo
- Publication number
- ES2656471T3 ES2656471T3 ES14728350.1T ES14728350T ES2656471T3 ES 2656471 T3 ES2656471 T3 ES 2656471T3 ES 14728350 T ES14728350 T ES 14728350T ES 2656471 T3 ES2656471 T3 ES 2656471T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- cyclopropyl
- chlorophenyl
- triazolo
- dihydropyrrolo
- 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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- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 15
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- -1 1,4-dimethyl-1 H -benzo- [d] [1,2,3] -triazol-6-yl Chemical group 0.000 claims description 68
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- ZRAGYVAOZMZDPY-UHFFFAOYSA-N 6-(4-chlorophenyl)-3-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-methyl-6h-pyrrolo[3,4-c]pyrazol-4-one Chemical compound C=1N2C(C)=NN=C2C(C)=CC=1N(C1=O)C(C=2C=CC(Cl)=CC=2)C(N(N=2)C)=C1C=2C1CC1 ZRAGYVAOZMZDPY-UHFFFAOYSA-N 0.000 claims description 6
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- ZBIYSSHSZQVNSP-GOSISDBHSA-N (6r)-6-(4-chlorophenyl)-3-cyclopropyl-5-[3-(difluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-1-methyl-6h-pyrrolo[3,4-c]pyrazol-4-one Chemical compound N=1N(C)C([C@H](N(C2=O)C=3C=C(C4=NN=C(N4C=3)C(F)F)C)C=3C=CC(Cl)=CC=3)=C2C=1C1CC1 ZBIYSSHSZQVNSP-GOSISDBHSA-N 0.000 claims 1
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- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- OEBIHOVSAMBXIB-SJKOYZFVSA-N selitrectinib Chemical compound C[C@@H]1CCC2=NC=C(F)C=C2[C@H]2CCCN2C2=NC3=C(C=NN3C=C2)C(=O)N1 OEBIHOVSAMBXIB-SJKOYZFVSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 238000004659 sterilization and disinfection Methods 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
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- 210000003932 urinary bladder Anatomy 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13169441 | 2013-05-28 | ||
| EP13169441 | 2013-05-28 | ||
| PCT/IB2014/061736 WO2014191906A1 (en) | 2013-05-28 | 2014-05-27 | Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease |
Publications (1)
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|---|---|
| ES2656471T3 true ES2656471T3 (es) | 2018-02-27 |
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| ES14728350.1T Active ES2656471T3 (es) | 2013-05-28 | 2014-05-27 | Derivados de pirazolo-pirrolidin-4-ona como inhibidores de BET y su uso en el tratamiento de enfermedades |
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| EP (1) | EP3004108B1 (enExample) |
| JP (1) | JP2016520118A (enExample) |
| KR (1) | KR20160012195A (enExample) |
| CN (1) | CN105263934B (enExample) |
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| EA (1) | EA028175B1 (enExample) |
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| MX (1) | MX2015016421A (enExample) |
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| PT (1) | PT3004108T (enExample) |
| WO (1) | WO2014191906A1 (enExample) |
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| MX366703B (es) | 2013-03-15 | 2019-07-22 | Incyte Holdings Corp | Heterociclos tricíclicos como inhibidores de la proteína bet. |
| MX2015016421A (es) | 2013-05-28 | 2016-03-03 | Novartis Ag | Derivados de pirazolo-pirrolidin-4-ona como inhibidores de bet y su uso en el tratamiento de enfermedades. |
| WO2015006193A1 (en) | 2013-07-08 | 2015-01-15 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| WO2015081189A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| US9399640B2 (en) | 2013-11-26 | 2016-07-26 | Incyte Corporation | Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors |
| US9309246B2 (en) | 2013-12-19 | 2016-04-12 | Incyte Corporation | Tricyclic heterocycles as BET protein inhibitors |
| SI3674302T1 (sl) | 2014-04-23 | 2023-07-31 | Incyte Holdings Corporation | 1h-pirolo(2,3-c)piridin-7(6h)-oni in pirazolo(3,4-c)piridin-7(6h)-oni kot zaviralci proteinov bet |
| ES2855225T3 (es) | 2014-09-15 | 2021-09-23 | Incyte Corp | Heterociclos tricíclicos para su uso como inhibidores de proteínas BET |
| GB201504694D0 (en) | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Covalent conjugates |
| US20170121347A1 (en) | 2015-10-29 | 2017-05-04 | Incyte Corporation | Amorphous solid form of a bet protein inhibitor |
| EP3416947A1 (en) | 2016-02-15 | 2018-12-26 | CeMM - Forschungszentrum für Molekulare Medizin GmbH | Taf1 inhibitors for the therapy of cancer |
| CR20190027A (es) | 2016-06-20 | 2019-05-16 | Incyte Corp | Formas sólidas cristalinas de un inhibidor de bet |
| JP2020511401A (ja) | 2016-11-14 | 2020-04-16 | チェム−フォルシュングスツェントルン フュル モレクラーレ メディツィン ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌の治療法のためのｂｒｄ４阻害剤と葉酸代謝拮抗薬との組み合わせ物 |
| US11466034B2 (en) | 2017-12-20 | 2022-10-11 | Betta Pharmaceuticals Co., Ltd. | Compound functioning as bromodomain protein inhibitor, and composition |
| CN112533620B (zh) * | 2018-03-05 | 2025-03-28 | 慕尼黑工业大学临床教学中心 | 通过溶瘤腺病毒和cdk4/6抑制剂的组合治疗肿瘤 |
| KR20220054293A (ko) * | 2019-07-12 | 2022-05-02 | 시닉 이뮤놀러지 비.브이. | Isoqc 및/또는 qc 효소의 억제제로서 n-치환된-3,4-(융합된 5-환)-5-페닐-피롤리딘-2-온 화합물 |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
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-
2014
- 2014-05-27 MX MX2015016421A patent/MX2015016421A/es unknown
- 2014-05-27 ES ES14728350.1T patent/ES2656471T3/es active Active
- 2014-05-27 PL PL14728350T patent/PL3004108T3/pl unknown
- 2014-05-27 AU AU2014272695A patent/AU2014272695B2/en not_active Ceased
- 2014-05-27 WO PCT/IB2014/061736 patent/WO2014191906A1/en not_active Ceased
- 2014-05-27 BR BR112015029401A patent/BR112015029401A8/pt not_active Application Discontinuation
- 2014-05-27 CA CA2912986A patent/CA2912986A1/en not_active Abandoned
- 2014-05-27 EP EP14728350.1A patent/EP3004108B1/en not_active Not-in-force
- 2014-05-27 EA EA201592255A patent/EA028175B1/ru not_active IP Right Cessation
- 2014-05-27 CN CN201480030590.0A patent/CN105263934B/zh not_active Expired - Fee Related
- 2014-05-27 JP JP2016516280A patent/JP2016520118A/ja active Pending
- 2014-05-27 US US14/892,623 patent/US9624247B2/en not_active Expired - Fee Related
- 2014-05-27 PT PT147283501T patent/PT3004108T/pt unknown
- 2014-05-27 KR KR1020157036224A patent/KR20160012195A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| CA2912986A1 (en) | 2014-12-04 |
| US9624247B2 (en) | 2017-04-18 |
| CN105263934A (zh) | 2016-01-20 |
| CN105263934B (zh) | 2017-09-08 |
| PT3004108T (pt) | 2018-01-24 |
| EA201592255A1 (ru) | 2016-04-29 |
| PL3004108T3 (pl) | 2018-03-30 |
| MX2015016421A (es) | 2016-03-03 |
| BR112015029401A2 (pt) | 2017-07-25 |
| AU2014272695B2 (en) | 2016-10-20 |
| EA028175B1 (ru) | 2017-10-31 |
| EP3004108A1 (en) | 2016-04-13 |
| US20160102107A1 (en) | 2016-04-14 |
| KR20160012195A (ko) | 2016-02-02 |
| AU2014272695A1 (en) | 2015-11-26 |
| WO2014191906A1 (en) | 2014-12-04 |
| BR112015029401A8 (pt) | 2020-03-17 |
| EP3004108B1 (en) | 2017-10-18 |
| JP2016520118A (ja) | 2016-07-11 |
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