BR112017004897A2 - compostos inovadores como inibidores rearranjados durante a transfecção (ret) - Google Patents
compostos inovadores como inibidores rearranjados durante a transfecção (ret)Info
- Publication number
- BR112017004897A2 BR112017004897A2 BR112017004897A BR112017004897A BR112017004897A2 BR 112017004897 A2 BR112017004897 A2 BR 112017004897A2 BR 112017004897 A BR112017004897 A BR 112017004897A BR 112017004897 A BR112017004897 A BR 112017004897A BR 112017004897 A2 BR112017004897 A2 BR 112017004897A2
- Authority
- BR
- Brazil
- Prior art keywords
- cancer
- functional
- ret
- disorders
- rearranged
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 3
- 238000001890 transfection Methods 0.000 title abstract 3
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 6
- 206010010774 Constipation Diseases 0.000 abstract 3
- 201000010099 disease Diseases 0.000 abstract 3
- 208000035475 disorder Diseases 0.000 abstract 3
- 206010012735 Diarrhoea Diseases 0.000 abstract 2
- 230000000694 effects Effects 0.000 abstract 2
- 208000004998 Abdominal Pain Diseases 0.000 abstract 1
- 208000001446 Anaplastic Thyroid Carcinoma Diseases 0.000 abstract 1
- 206010002240 Anaplastic thyroid cancer Diseases 0.000 abstract 1
- 206010004593 Bile duct cancer Diseases 0.000 abstract 1
- 208000003174 Brain Neoplasms Diseases 0.000 abstract 1
- 206010006187 Breast cancer Diseases 0.000 abstract 1
- 208000026310 Breast neoplasm Diseases 0.000 abstract 1
- 206010009944 Colon cancer Diseases 0.000 abstract 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 abstract 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 abstract 1
- 201000001342 Fallopian tube cancer Diseases 0.000 abstract 1
- 208000013452 Fallopian tube neoplasm Diseases 0.000 abstract 1
- 206010016935 Follicular thyroid cancer Diseases 0.000 abstract 1
- 208000018522 Gastrointestinal disease Diseases 0.000 abstract 1
- 206010018338 Glioma Diseases 0.000 abstract 1
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 208000008839 Kidney Neoplasms Diseases 0.000 abstract 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract 1
- 208000009018 Medullary thyroid cancer Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 206010029260 Neuroblastoma Diseases 0.000 abstract 1
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- 206010033701 Papillary thyroid cancer Diseases 0.000 abstract 1
- 206010060862 Prostate cancer Diseases 0.000 abstract 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 abstract 1
- 208000009956 adenocarcinoma Diseases 0.000 abstract 1
- 230000004064 dysfunction Effects 0.000 abstract 1
- 201000004101 esophageal cancer Diseases 0.000 abstract 1
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- 201000010536 head and neck cancer Diseases 0.000 abstract 1
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- 206010073071 hepatocellular carcinoma Diseases 0.000 abstract 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 230000000968 intestinal effect Effects 0.000 abstract 1
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract 1
- 229940043355 kinase inhibitor Drugs 0.000 abstract 1
- 201000005202 lung cancer Diseases 0.000 abstract 1
- 208000020816 lung neoplasm Diseases 0.000 abstract 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 230000004899 motility Effects 0.000 abstract 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 abstract 1
- 238000010606 normalization Methods 0.000 abstract 1
- 201000002628 peritoneum cancer Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
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- 230000008961 swelling Effects 0.000 abstract 1
- 208000011580 syndromic disease Diseases 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 abstract 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 abstract 1
- 208000019179 thyroid gland undifferentiated (anaplastic) carcinoma Diseases 0.000 abstract 1
- 206010044412 transitional cell carcinoma Diseases 0.000 abstract 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 abstract 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 abstract 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- 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
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- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- C07D213/65—One oxygen atom attached in position 3 or 5
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- C07D213/62—Oxygen or sulfur atoms
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- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
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- C07—ORGANIC CHEMISTRY
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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- 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
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
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| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| EA032030B1 (ru) | 2014-09-10 | 2019-03-29 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Соединения в качестве ингибиторов реаранжированной во время трансфекции (ret) киназы |
| PT3191450T (pt) | 2014-09-10 | 2019-05-29 | Glaxosmithkline Ip Dev Ltd | Derivados de piridona como inibidores da quinase rearranjada durante a transfecção (ret) |
| WO2016127074A1 (en) | 2015-02-06 | 2016-08-11 | Blueprint Medicines Corporation | 2-(pyridin-3-yl)-pyrimidine derivatives as ret inhibitors |
| RS61485B1 (sr) | 2015-07-16 | 2021-03-31 | Array Biopharma Inc | Supstituisana pirazolo [1,5-a] piridinska jedinjenja kao inhibitori ret kinaze |
| IL302209B2 (en) | 2015-11-02 | 2024-06-01 | Blueprint Medicines Corp | Inhibitors of ret |
| WO2017145050A1 (en) * | 2016-02-23 | 2017-08-31 | Glaxosmithkline Intellectual Property Development Limited | Pyridylpyridone derivative useful as a ret kinase inhibitor in the treatment of ibs and cancer |
| WO2017152126A1 (en) * | 2016-03-03 | 2017-09-08 | Cornell University | Small molecule ire1-alpha inhibitors |
| WO2017161269A1 (en) | 2016-03-17 | 2017-09-21 | Blueprint Medicines Corporation | Inhibitors of ret receptor tyrosine kinases |
| WO2018017983A1 (en) | 2016-07-22 | 2018-01-25 | Blueprint Medicines Corporation | Compounds useful for treating disorders related to ret |
| JP2018052878A (ja) * | 2016-09-29 | 2018-04-05 | 第一三共株式会社 | ピリジン化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| TWI795381B (zh) | 2016-12-21 | 2023-03-11 | 比利時商健生藥品公司 | 作為malt1抑制劑之吡唑衍生物 |
| EP3571203B1 (en) | 2017-01-18 | 2023-06-07 | Array BioPharma Inc. | Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CN110891573A (zh) | 2017-05-15 | 2020-03-17 | 缆图药品公司 | Ret抑制剂和mtorc1抑制剂的组合及其用于治疗由异常ret活性介导的癌症的用途 |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| CN111615514B (zh) | 2018-01-18 | 2022-10-11 | 奥瑞生物药品公司 | 作为ret激酶抑制剂的取代的吡唑并[4,3-c]吡啶化合物 |
| PT3773589T (pt) | 2018-04-03 | 2024-02-06 | Blueprint Medicines Corp | Inibidor de ret para utilização no tratamento de cancro com alteração de ret |
| CN109096264B (zh) * | 2018-08-28 | 2019-08-23 | 山东理工职业学院 | Ret抑制剂及其制备方法、组合物和用途 |
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| WO2020083311A1 (zh) * | 2018-10-24 | 2020-04-30 | 南京明德新药研发有限公司 | 作为ret抑制剂的吡嗪衍生物 |
| CN109678724A (zh) * | 2018-12-18 | 2019-04-26 | 常州大学 | 一种2-甲基-1-取代苯基-2-丙胺类化合物的新合成方法 |
| US12404260B2 (en) | 2019-04-11 | 2025-09-02 | Janssen Pharmaceutica Nv | Pyridine rings containing derivatives as MALT1 inhibitors |
| EP4021894A1 (en) | 2019-08-30 | 2022-07-06 | University of Rochester | Septin inhibitors for treatment of cancers |
| CN110950898B (zh) * | 2019-12-12 | 2022-11-11 | 江苏华益科技有限公司 | 一种含氮的氘代甲基化合物的合成方法 |
| CN111187257B (zh) * | 2020-02-17 | 2021-03-16 | 山东理工职业学院 | Ret受体酪氨酸激酶抑制剂 |
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| BR112023025083A2 (pt) | 2021-06-02 | 2024-02-27 | Fmc Corp | Piridinas fundidas para controlar pragas invertebradas |
| CN113896650A (zh) * | 2021-10-27 | 2022-01-07 | 成都科圣原医药科技有限公司 | 一种辛波莫德中间体的合成方法 |
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| MXPA00006233A (es) | 1997-12-22 | 2002-09-18 | Bayer Ag | Inhibicion de la actividad de la cinasa p38 utilizando ureas heterociclicas sustituidas. |
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| US20070244120A1 (en) * | 2000-08-18 | 2007-10-18 | Jacques Dumas | Inhibition of raf kinase using substituted heterocyclic ureas |
| SK1812002A3 (en) | 1999-08-12 | 2003-02-04 | Pharmacia Italia Spa | 3(5)-Amino-pyrazole derivatives, process for their preparation and their use as antitumor agents |
| AU2002215053A1 (en) | 2000-11-27 | 2002-06-24 | Pharmacia Italia S.P.A. | Phenylacetamido- pyrazole derivatives and their use as antitumor agents |
| DE10201764A1 (de) | 2002-01-18 | 2003-07-31 | Bayer Cropscience Ag | Substituierte 4-Aminopyridin-Derivate |
| AR037647A1 (es) | 2002-05-29 | 2004-12-01 | Novartis Ag | Derivados de diarilurea utiles para el tratamiento de enfermedades dependientes de la cinasa de proteina |
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| JP2010506879A (ja) | 2006-10-16 | 2010-03-04 | ノバルティス アーゲー | プロテインキナーゼ阻害剤として有用なフェニルアセトアミド |
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| PT2970191T (pt) | 2013-03-15 | 2017-03-23 | Glaxosmithkline Ip Dev Ltd | Derivados de piridina como inibidores da quinase rearranjada durante transfecção(ret) |
| US8937071B2 (en) | 2013-03-15 | 2015-01-20 | Glaxosmithkline Intellectual Property Development Limited | Compounds as rearranged during transfection (RET) inhibitors |
| EA032030B1 (ru) | 2014-09-10 | 2019-03-29 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Соединения в качестве ингибиторов реаранжированной во время трансфекции (ret) киназы |
| PT3191450T (pt) * | 2014-09-10 | 2019-05-29 | Glaxosmithkline Ip Dev Ltd | Derivados de piridona como inibidores da quinase rearranjada durante a transfecção (ret) |
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| US9879021B2 (en) | 2018-01-30 |
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| WO2016037578A1 (en) | 2016-03-17 |
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| EP3191449A4 (en) | 2018-04-25 |
| CN107250110A (zh) | 2017-10-13 |
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| AU2015316438B2 (en) | 2018-05-24 |
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| US20170298074A1 (en) | 2017-10-19 |
| CR20170094A (es) | 2017-05-08 |
| DK3191449T3 (da) | 2020-08-03 |
| CN107250110B (zh) | 2020-04-24 |
| JP6538153B2 (ja) | 2019-07-03 |
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| MY187169A (en) | 2021-09-07 |
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| SG11201701695UA (en) | 2017-04-27 |
| ES2819871T3 (es) | 2021-04-19 |
| CA2960730A1 (en) | 2016-03-17 |
| PE20170677A1 (es) | 2017-05-13 |
| EP3191449A1 (en) | 2017-07-19 |
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