AR082986A1 - DERIVADOS DE PURINA COMO INHIBIDORES DE PI3K-d, METODOS PARA SU PREPARACION, FORMULACIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN EL TRATAMIENTO DE ENFERMEDADES HIPERPROLIFERATIVAS - Google Patents
DERIVADOS DE PURINA COMO INHIBIDORES DE PI3K-d, METODOS PARA SU PREPARACION, FORMULACIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN EL TRATAMIENTO DE ENFERMEDADES HIPERPROLIFERATIVASInfo
- Publication number
- AR082986A1 AR082986A1 ARP110103346A ARP110103346A AR082986A1 AR 082986 A1 AR082986 A1 AR 082986A1 AR P110103346 A ARP110103346 A AR P110103346A AR P110103346 A ARP110103346 A AR P110103346A AR 082986 A1 AR082986 A1 AR 082986A1
- Authority
- AR
- Argentina
- Prior art keywords
- optionally substituted
- alkyl
- hydrogen
- phenyl
- substituted
- Prior art date
Links
- 201000010099 disease Diseases 0.000 title abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 2
- 238000000034 method Methods 0.000 title abstract 2
- 230000003463 hyperproliferative effect Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000003212 purines Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract 5
- 239000001257 hydrogen Substances 0.000 abstract 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 5
- 125000005843 halogen group Chemical group 0.000 abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 4
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 4
- -1 1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo [3,4-c] pyridinyl Chemical group 0.000 abstract 3
- 125000001072 heteroaryl group Chemical group 0.000 abstract 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 3
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 2
- 229910052799 carbon Inorganic materials 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 125000001188 haloalkyl group Chemical group 0.000 abstract 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 abstract 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 abstract 1
- 125000002541 furyl group Chemical group 0.000 abstract 1
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 125000001041 indolyl group Chemical group 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 125000001715 oxadiazolyl group Chemical group 0.000 abstract 1
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 125000004076 pyridyl group Chemical group 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000005017 substituted alkenyl group Chemical group 0.000 abstract 1
- 125000005415 substituted alkoxy group Chemical group 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 125000001425 triazolyl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- 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
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Métodos de preparación y uso de los compuestos en el tratamiento del cáncer y otras enfermedades.Reivindicación 1: Un compuesto de la fórmula (1) o uno de sus estereoisómeros o una mezcla de sus estereoisómeros, opcionalmente como una de sus sales farmacéuticamente aceptable, en donde R1 es alquilo, haloalquilo o cicloalquilo opcionalmente sustituido; el resto de fórmula (2) es un anillo de 4, 5, 6 ó 7 miembros, en donde: R2 en cada aparición es, de modo independiente, halo, hidroxi, alquilo, alcoxi, hidroxialquilo, haloalcoxi o -C(O)O-alquilo o dos grupos R2 se pueden unir con carbonos a los que están unidos para formar un anillo bicíclico en puente o fusionado; n es 0, 1, 2 ó 3; X es C o N; en donde: cuando X es N: R3 está ausente; R3’ es arilo o heteroarilo opcionalmente sustituido con uno o dos grupos seleccionados, de modo independiente, de heteroarilalquiloxi; alquilo sustituido con arilsulfonilamino; alquilo sustituido con cicloalquilcarbonilamino; o R3’ es -SO2-Ra, en donde Ra es alquilo opcionalmente sustituido, fenilo opcionalmente sustituido, fenilalquilo opcionalmente sustituido o heteroarilo opcionalmente sustituido; cuando X es C: R3 es ciano, aminoalquilo, alcoxi, carbonilo o hidroxi y R3’ es un fenilo opcionalmente sustituido; o R3 es hidrógeno y R3’ es fenilo, alquilo sustituido con 1-fenil-4,5,6,7-tetrahidro-1H-pirazolo[3,4-c]piridinilo, indolilo opcionalmente sustituido, 1H-benzo[d][1,2,3]triazolilo opcionalmente sustituido, oxoindolinilo opcionalmente sustituido, benzoimidazolilo opcionalmente sustituido, piridinilo opcionalmente sustituido (oxadiazolilo sustituido con furanilo), 2-oxo-3,4-dihidroquinazolinilo, -C(O)NRbRc, en donde Rb es hidrógeno o alquilo; y Rc es heteroarilalquilo opcionalmente sustituido; o R3 es hidrógeno y R3’ es un grupo de la fórmula (a), (b), (c), (d), (e) ó (f), en donde: Z1 es O, NH o N opcionalmente sustituido con aminoalquilo, alquilaminoalquilo o dialquilaminoalquilo; Z2 es CH o N; A es N C-H o C-Rd; cada Rd, cuando está presente, es, de modo independiente, halo, alquilo, alcoxi opcionalmente sustituido o heterocicloalquilo opcionalmente sustituido y Re es amino o haloalquilo; o R3 y R3’ se toman junto con el carbono al que están unidos para formar un anillo opcionalmente sustituido de 5 ó 6 miembros de fórmula (g), (h), (i), (j), (k) ó (l), en donde: Z3 es CH2 o NH; Z4 es NRf o CRf y Rf es fenilo opcionalmente sustituido; Y está ausente o es halo, alquilo, -(C=O)-, -NRx(C=O)- o -(C=O)NRx-, -O-(C=O)-, -(C=O)O-, -NRx-(C=O)O- u -O(C=O)NRx-, en donde Rx es hidrógeno o alquilo opcionalmente sustituido; R4 es hidrógeno, halo, alquilo opcionalmente sustituido, alquenilo opcionalmente sustituido, arilo opcionalmente sustituido, cicloalquilo opcionalmente sustituido, heterocicloalquilo opcionalmente sustituido, heteroarilo opcionalmente sustituido; y cuando Y es -N(Rx)-(C=O)- o -(C=O)-N(Rx)-, Rx y R4 se pueden unir junto con los átomos a los que están unidos para formar un anillo de 4, 5 ó 6 miembros, que opcionalmente contiene 1 ó 2 heteroátomos adicionales seleccionados de N, S y O.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38288410P | 2010-09-14 | 2010-09-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR082986A1 true AR082986A1 (es) | 2013-01-23 |
Family
ID=44898157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP110103346A AR082986A1 (es) | 2010-09-14 | 2011-09-14 | DERIVADOS DE PURINA COMO INHIBIDORES DE PI3K-d, METODOS PARA SU PREPARACION, FORMULACIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN EL TRATAMIENTO DE ENFERMEDADES HIPERPROLIFERATIVAS |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9346807B2 (es) |
| EP (1) | EP2616469B1 (es) |
| JP (1) | JP5954838B2 (es) |
| AR (1) | AR082986A1 (es) |
| AU (1) | AU2011302124B2 (es) |
| CA (1) | CA2812091C (es) |
| ES (1) | ES2612503T3 (es) |
| TW (1) | TWI617560B (es) |
| WO (1) | WO2012037226A1 (es) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011302196B2 (en) | 2010-09-14 | 2016-04-28 | Exelixis, Inc. | Inhibitors of PI3K-delta and methods of their use and manufacture |
| WO2013067141A1 (en) | 2011-11-01 | 2013-05-10 | Exelixis, Inc. | N- (3- { [ (3- { [2-chloro-5- (methoxy) phenyl] amino} quinoxalin- 2 -yl) amino] sulfonyl} phe nyl) - 2 -methylalaninamide as phosphatidylinositol 3 - kinase inhibitor for the treatment of lymphoproliferative malignancies |
| DK2790705T3 (en) | 2011-12-15 | 2018-03-12 | Novartis Ag | Use of inhibitors of the activity or function of PI3K |
| GB201211021D0 (en) * | 2012-06-21 | 2012-08-01 | Cancer Rec Tech Ltd | Pharmaceutically active compounds |
| US9737521B2 (en) | 2012-11-08 | 2017-08-22 | Rhizen Pharmaceuticals Sa | Pharmaceutical compositions containing a PDE4 inhibitor and a PI3 delta or dual PI3 delta-gamma kinase inhibitor |
| CN104918939B (zh) * | 2012-11-16 | 2018-08-28 | 默沙东公司 | 人磷脂酰肌醇3-激酶δ的嘌呤抑制剂 |
| CN104918940B (zh) * | 2012-11-16 | 2017-03-08 | 默沙东公司 | 人磷脂酰肌醇3‑激酶δ的嘌呤抑制剂 |
| EP2948447B1 (en) * | 2013-01-23 | 2016-09-21 | Astrazeneca AB | Chemical compounds |
| CN104513254B (zh) | 2013-09-30 | 2019-07-26 | 上海璎黎药业有限公司 | 稠合嘧啶类化合物、中间体、其制备方法、组合物和应用 |
| CN106831722B (zh) | 2013-10-16 | 2019-08-30 | 上海璎黎药业有限公司 | 稠合杂环化合物、其制备方法、药物组合物和用途 |
| SG11201607586UA (en) * | 2014-03-13 | 2016-10-28 | Agency Science Tech & Res | Fused pyrimidine-based hydroxamate derivatives |
| EP3119397B1 (en) | 2014-03-19 | 2022-03-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| SG11201700777VA (en) | 2014-08-04 | 2017-02-27 | Nuevolution As | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
| MX2017012390A (es) | 2015-03-30 | 2018-01-26 | Daiichi Sankyo Co Ltd | Derivados de 6-morfolinil-2-pirazolil-9h-purina y su uso como inhibidores de fosfoinositol-3-cinasa (pi3k). |
| WO2017000125A1 (en) * | 2015-06-29 | 2017-01-05 | Merck Sharp & Dohme Corp. | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
| CN114230571B (zh) | 2015-09-14 | 2025-07-08 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| JP6990657B2 (ja) * | 2016-02-08 | 2022-01-13 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | Ｄｄｒ１阻害剤としてのスピロインドリノン |
| WO2017166104A1 (en) * | 2016-03-30 | 2017-10-05 | Merck Sharp & Dohme Corp. | Purine inhibitors of human phosphatidylinositol 3-kinase delta |
| KR102399639B1 (ko) | 2016-12-02 | 2022-05-18 | 다이이찌 산쿄 가부시키가이샤 | 신규 엔도-β-N-아세틸글루코사미니다아제 |
| SG11202000143PA (en) | 2017-07-10 | 2020-02-27 | Celgene Corp | Antiproliferative compounds and methods of use thereof |
| US11685727B2 (en) | 2019-12-20 | 2023-06-27 | Nuevolution A/S | Compounds active towards nuclear receptors |
| JP2021098692A (ja) | 2019-12-20 | 2021-07-01 | ヌエヴォリューション・アクティーゼルスカブＮｕｅｖｏｌｕｔｉｏｎ Ａ／Ｓ | 核内受容体に対して活性の化合物 |
| MX2022012260A (es) | 2020-03-31 | 2022-11-30 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
| JP7713954B2 (ja) | 2020-03-31 | 2025-07-28 | ヌエヴォリューション・アクティーゼルスカブ | 核内受容体に対して活性な化合物 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4107288A (en) | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| ES2356886T3 (es) * | 1998-03-31 | 2011-04-14 | Kyowa Hakko Kirin Co., Ltd. | Compuestos heterocíclicos nitrogenados. |
| US20080233127A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors |
| WO2009045174A1 (en) | 2007-10-05 | 2009-04-09 | S*Bio Pte Ltd | 2-morpholinylpurines as inhibitors of pi3k |
| US20110230464A1 (en) * | 2007-10-26 | 2011-09-22 | Paul Goldsmith | Purine derivatives useful as p13 kinase inhibitors |
| KR20110042153A (ko) * | 2008-05-30 | 2011-04-25 | 제넨테크, 인크. | 퓨린 ｐｉ３ｋ 억제 화합물 및 사용 방법 |
| US20110105500A1 (en) * | 2008-06-27 | 2011-05-05 | S*Bio Pte Ltd. | Pyrazine substituted purines |
| EP2307414A4 (en) * | 2008-07-07 | 2011-10-26 | Xcovery Holding Co Llc | SELECTIVE INHIBITORS OF PI3 KINASE ISOFORMS |
-
2011
- 2011-09-14 AU AU2011302124A patent/AU2011302124B2/en not_active Ceased
- 2011-09-14 JP JP2013529290A patent/JP5954838B2/ja not_active Expired - Fee Related
- 2011-09-14 US US13/822,840 patent/US9346807B2/en active Active
- 2011-09-14 TW TW100133028A patent/TWI617560B/zh not_active IP Right Cessation
- 2011-09-14 EP EP11776614.7A patent/EP2616469B1/en active Active
- 2011-09-14 ES ES11776614.7T patent/ES2612503T3/es active Active
- 2011-09-14 CA CA2812091A patent/CA2812091C/en active Active
- 2011-09-14 WO PCT/US2011/051563 patent/WO2012037226A1/en not_active Ceased
- 2011-09-14 AR ARP110103346A patent/AR082986A1/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| US20140058103A1 (en) | 2014-02-27 |
| TW201219391A (en) | 2012-05-16 |
| JP2013537231A (ja) | 2013-09-30 |
| EP2616469B1 (en) | 2016-10-26 |
| JP5954838B2 (ja) | 2016-07-20 |
| CA2812091C (en) | 2020-03-24 |
| US9346807B2 (en) | 2016-05-24 |
| TWI617560B (zh) | 2018-03-11 |
| AU2011302124B2 (en) | 2016-03-17 |
| AU2011302124A1 (en) | 2013-04-04 |
| WO2012037226A1 (en) | 2012-03-22 |
| ES2612503T3 (es) | 2017-05-17 |
| CA2812091A1 (en) | 2012-03-22 |
| EP2616469A1 (en) | 2013-07-24 |
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