HRP20161463T1 - Dimerni spojevi kao agonisti receptora fgf (fgfr), postupak za njihovu pripravu i njihova terapijska uporaba - Google Patents
Dimerni spojevi kao agonisti receptora fgf (fgfr), postupak za njihovu pripravu i njihova terapijska uporaba Download PDFInfo
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- HRP20161463T1 HRP20161463T1 HRP20161463TT HRP20161463T HRP20161463T1 HR P20161463 T1 HRP20161463 T1 HR P20161463T1 HR P20161463T T HRP20161463T T HR P20161463TT HR P20161463 T HRP20161463 T HR P20161463T HR P20161463 T1 HRP20161463 T1 HR P20161463T1
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- 150000001875 compounds Chemical class 0.000 title claims 18
- 108091008794 FGF receptors Proteins 0.000 title claims 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 title claims 2
- 238000002360 preparation method Methods 0.000 title claims 2
- 239000000556 agonist Substances 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims 10
- 239000002253 acid Substances 0.000 claims 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 claims 3
- -1 3-phenyl-1H-pyrazolo[3,4-b]pyridine-4,6-diyl Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 239000000178 monomer Substances 0.000 claims 3
- 230000004083 survival effect Effects 0.000 claims 3
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- YPFIEFINFLROIN-UHFFFAOYSA-N 5-[4-[2-[2-[2-[2-[2-[[6-(3-carboxy-4-fluorophenyl)-3-phenyl-2h-pyrazolo[3,4-b]pyridine-4-carbonyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethylcarbamoyl]-3-phenyl-2h-pyrazolo[3,4-b]pyridin-6-yl]-2-fluorobenzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(C2=NC3=NNC(=C3C(C(=O)NCCOCCOCCOCCOCCNC(=O)C=3C4=C(C=5C=CC=CC=5)NN=C4N=C(C=3)C=3C=C(C(F)=CC=3)C(O)=O)=C2)C=2C=CC=CC=2)=C1 YPFIEFINFLROIN-UHFFFAOYSA-N 0.000 claims 1
- GOLBJTJSBCKURI-UHFFFAOYSA-N 5-[4-[5-[2-[2-[3-[[6-(3-carboxy-4-fluorophenyl)-3-phenyl-2H-pyrazolo[3,4-b]pyridine-4-carbonyl]amino]propoxy]ethoxy]ethoxy]pentanoyl]-3-phenyl-2H-pyrazolo[3,4-b]pyridin-6-yl]-2-fluorobenzoic acid Chemical compound C(=O)(O)C=1C=C(C=CC=1F)C1=CC(=C2C(=N1)NN=C2C1=CC=CC=C1)C(CCCCOCCOCCOCCCNC(=O)C1=C2C(=NC(=C1)C=1C=CC(=C(C(=O)O)C=1)F)NN=C2C1=CC=CC=C1)=O GOLBJTJSBCKURI-UHFFFAOYSA-N 0.000 claims 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 208000033386 Buerger disease Diseases 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 1
- 201000007737 Retinal degeneration Diseases 0.000 claims 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims 1
- 206010043540 Thromboangiitis obliterans Diseases 0.000 claims 1
- 206010052428 Wound Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 1
- 238000002399 angioplasty Methods 0.000 claims 1
- 206010003230 arteritis Diseases 0.000 claims 1
- 210000001367 artery Anatomy 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 210000003780 hair follicle Anatomy 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000005304 joining Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000009756 muscle regeneration Effects 0.000 claims 1
- 210000003098 myoblast Anatomy 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 201000008482 osteoarthritis Diseases 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 208000033808 peripheral neuropathy Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 201000011461 pre-eclampsia Diseases 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 230000004258 retinal degeneration Effects 0.000 claims 1
- 230000000250 revascularization Effects 0.000 claims 1
- 208000001076 sarcopenia Diseases 0.000 claims 1
- 230000020341 sensory perception of pain Effects 0.000 claims 1
- 210000002460 smooth muscle Anatomy 0.000 claims 1
- 210000005070 sphincter Anatomy 0.000 claims 1
- 231100000216 vascular lesion Toxicity 0.000 claims 1
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- C07D401/14—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 containing three or more hetero rings
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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
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- 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
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Claims (15)
1. Spojevi koji odgovaraju općoj formuli:
M1-L-M2
u kojoj M1 i M2, koji mogu biti identični ili različiti, svaki predstavljaju, međusobno neovisno, monomernu jedinicu M i L predstavlja skupinu poveznicu koja kovalentno povezuje M1 i M2, naznačen time da navedena monomerna jedinica odgovara općoj formuli M kako slijedi:
[image]
u kojoj:
- zvjezdica * ukazuje na mjesto vezivanja između monomera i poveznice L, navedeno mjesto vezivanja svake monomerne jedinice M1 i M2 je smješteno na jednom od supstituenata R ili R2,
- R predstavlja vodikov atom (u kojem slučaju mjesto vezivanja L sa M je smješteno na R2) ili skupinu -CONH*,
- R1 predstavlja vodikov atom ili nerazgranatu skupinu (Cl-C3)alkil,
- R2 predstavlja skupinu -CONH2 (u kojem slučaju mjesto vezivanja L sa M je smješteno na R) ili -CONH*,
- R3 predstavlja skupinu -CO2R4, gdje R4 predstavlja vodikov atom ili nerazgranatu skupinu (C1-C4)alkil,
- X je atom halogena odabran od atoma fluora, klora i broma,
- L predstavlja slijedeće PEG radikale:
[image]
[image]
u kojima
- zvjezdica * označava atom za povezivanje L s monomernom jedinicom M na supstituentu R* ili R2*;
- n predstavlja cijeli broj 2 do 6,
u obliku baze ili adicijske soli s kiselinom ili s bazom.
2. Spojevi prema zahtjevu 1, naznačeni time da R1 predstavlja vodikov atom, u obliku baze ili adicijske soli s kiselinom ili s bazom.
3. Spojevi u skladu s bilo kojim od prethodnih zahtjeva, naznačeni time da R3 predstavlja skupinu -CO2R4, gdje R4 predstavlja vodikov atom, u obliku baze ili adicijske soli s kiselinom ili s bazom.
4. Spojevi prema jednom od prethodnih zahtjeva, naznačeni time da X predstavlja fluorov atom, u obliku baze ili adicijske soli s kiselinom ili s bazom.
5. Spojevi prema jednom od zahtjeva 1 do 4, naznačeni time da:
- R predstavlja skupinu -CONH*, gdje zvjezdica * označava mjesto spajanja L, prvo, s monomernom jedinicom M, te zatim s monomernom jedinicom M2,
- R1 predstavlja vodikov atom ili nerazgranatu skupinu (Cl-C3)alkil, u obliku baze ili adicijske soli s kiselinom ili s bazom.
6. Spojevi prema jednom od zahtjeva 1 do 5, naznačeni time da se R nalazi u meta ili para položaju, u obliku baze ili adicijske soli s kiselinom ili s bazom.
7. Spojevi prema jednom od zahtjeva 1 do 4, naznačeni time da:
- R predstavlja vodikov atom,
- R2 predstavlja skupinu -CONH*, gdje zvjezdica * označava mjesto spajanja L, prvo, s monomernom jedinicom M1, te zatim, s monomernom jedinicom M2, u obliku baze ili adicijske soli s kiselinom ili s bazom.
8. Spojevi prema bilo kojem od zahtjeva 1 do 7, naznačeni time da n je cijeli broj 3 ili 4, u obliku baze ili adicijske soli s kiselinom ili s bazom.
9. Spoj prema bilo kojem od prethodnih zahtjeva, naznačen time da je odabran iz skupa koji čine:
Spoj br. 1: 3,3'-{etan-1,2-diilbis[oksipropan-3,1-diilkarbamoil(3-fenil-1H-pirazolo[3,4-b]piridin-4,6-diil)]}bis(6-fluorobenzojeva kiselina);
Spoj br. 2: 5-[4-({15-[6-(3-karboksi-4-fluorofenil)-3-fenil-1H-pirazolo[3,4-b]piridin-4-il]-15-okso-4,7,10-trioksa-4-azapentadek-1-il}karbamoil)-3-fenil-1H-pirazolo[3,4-b]piridin-6-il]-2-fluorobenzojeva kiselina;
Spoj br. 3: 5-[4-({16-[6-(3-karboksi-4-fluorofenil)-3-fenil-1H-pirazolo[3,4-b]piridin-4-il]-16-okso-3,6,9,12-tetraoksa-15-azaheksadek-1-il}karbamoil)-3-fenil-1H-pirazolo[3,4-b]piridin-6-il]-2-fluorobenzojeva kiselina;
Spoj br. 4: 5-[4-({19-[6-(3-karboksi-4-fluorofenil)-3-fenil-1H-pirazolo[3,4-b]piridin-4-il]-19-okso-3,6,9,12,15-pentaoksa-18-azanonadek-1-il}karbamoil)-3-fenil-1H-pirazolo[3,4-b]piridin-6-il]-2-fluorobenzojeva kiselina;
Spoj br. 5: 5-[4-({21-[6-(3-karboksi-4-fluorofenil)-3-fenil-1H-pirazolo[3,4-b]piridin-4-il]-21-okso-4,7,10,13,16-pentaoksa-20-azahenikos-1-il}karbamoil)-3-fenil-1H-pirazolo[3,4-b]piridin-6-il]-2-fluorobenzojeva kiselina;
Spoj br. 6: 5-(4-karbamoil-3-{3-[(15-{3-[4-karbamoil-6-(3-karboksi-4-fluorofenil)-1H-pirazolo[3,4-b]piridin-3-il]fenil}-15-okso-4,7,10-trioksa-14-azapentadek-1-il)karbamoil]fenil}-1H-pirazolo[3,4-b]piridin-6-il)-2-fluorobenzojeva kiselina;
Spoj br. 7: 3,3'-{etan-1,2-diilbis[oksietan-2,1-diilkarbamoilbenzen-3,1-diil(4-karbamoil-1H-pirazolo[3,4-b]piridin-3,6-diil)]}bis(6-fluorobenzojeva kiselina);
Spoj br. 8: 5-(4-karbamoil-3-{4-[(15-{4-[4-karbamoil-6-(3-karboksi-4-fluorofenil)-1H-pirazolo[3,4-b]piridin-3-il]fenil}-15-okso-4,7,10-trioksa-14-azapentadek-1-il)karbamoil]fenil}-1H-pirazolo[3,4-b]piridin-6-il)-2-fluorobenzojeva kiselina;
Spoj br. 9: 3,3'-{etan-1,2-diilbis[oksietan-2,1-diilkarbamoilbenzen-4,1-diil(4-karbamoil-1H-pirazolo[3,4-b]piridin-3,6-diil)]}bis(6-fluorobenzojeva kiselina).
10. Postupak za pripremanje spojeva prema bilo kojem od zahtjeva 1 do 9, naznačen time da sadrži reakciju barem jednog monomera koji sadrži barem jednu skupinu karboksilne kiseline s reaktantom s formulom H2N-L-NH2 nakon aktivacije.
11. Lijek, naznačen time da sadrži spoj prema bilo kojem od zahtjeva 1 do 9, ili adicijsku sol tog spoja s farmaceutski prihvatljivom kiselinom ili bazom.
12. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time da je za uporabu kao lijek.
13. Farmaceutski pripravak, naznačen time da sadrži spoj prema bilo kojem od zahtjeva 1 do 9, ili farmaceutski prihvatljivu sol tog spoja, te također barem jedno farmaceutski prihvatljivo pomoćno sredstvo.
14. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time da je za uporabu za pripremanje lijeka namijenjenog za liječenje bolesti koje zahtijevaju aktivaciju FGF receptora.
15. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time da je za njegovu uporabu za liječenje srčane ishemije, liječenje bolesti povezanih sa sužavanjem ili začepljenjem arterija ili arteritisa, liječenje angine pektoris, liječenje tromboangiitis obliterans, liječenje ateroskleroze, liječenje radi inhibicije restenoze nakon angioplastike ili nakon endoarterektomije, liječenje rana, liječenje radi regeneracije mišića, liječenje radi preživljavanja mioblasta, liječenje sarkopenije, gubitka funkcionalnosti glatkih mišića sfinktera, liječenje nocicepcije i za liječenje kronične boli, liječenje periferne neuropatije, liječenje radi poboljšavanja preživljavanja bioumjetnog presatka gušterače kod pacijenata s dijabetesom, liječenje radi snižavanja razine kolesterola povezanog sa smanjenjem pretilosti, liječenje radi poboljšavanja revaskularizacije presatka i preživljavanja presatka, liječenje degeneracije mrežnice, liječenje pigmentnog retinitisa, liječenje osteoartritisa, liječenje preeklampsije, liječenje vaskularnih lezija i akutnog sindroma respiratornog distresa, liječenje radi zaštite kostiju, ili liječenje radi zaštite folikula kose.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| FR1162485A FR2985257B1 (fr) | 2011-12-28 | 2011-12-28 | Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique |
| PCT/IB2012/057727 WO2013098764A1 (en) | 2011-12-28 | 2012-12-26 | Fgf receptor (fgfr) agonist dimeric compounds, process for the preparation thereof and therapeutic use thereof |
| EP12824734.3A EP2797917B1 (en) | 2011-12-28 | 2012-12-26 | Fgf receptor (fgfr) agonist dimeric compounds, process for the preparation thereof and therapeutic use thereof |
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| HRP20161463T1 true HRP20161463T1 (hr) | 2016-12-16 |
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| EP (1) | EP2797917B1 (hr) |
| JP (1) | JP6049756B2 (hr) |
| KR (1) | KR20140105578A (hr) |
| CN (1) | CN104136434B (hr) |
| AR (1) | AR089452A1 (hr) |
| AU (1) | AU2012360095B2 (hr) |
| BR (1) | BR112014015882A8 (hr) |
| CA (1) | CA2861718C (hr) |
| CY (1) | CY1119301T1 (hr) |
| DK (1) | DK2797917T3 (hr) |
| ES (1) | ES2602798T3 (hr) |
| FR (1) | FR2985257B1 (hr) |
| HK (1) | HK1198649A1 (hr) |
| HR (1) | HRP20161463T1 (hr) |
| HU (1) | HUE029515T2 (hr) |
| IL (1) | IL233324A (hr) |
| LT (1) | LT2797917T (hr) |
| MX (1) | MX356656B (hr) |
| PL (1) | PL2797917T3 (hr) |
| PT (1) | PT2797917T (hr) |
| RU (1) | RU2014131065A (hr) |
| SG (1) | SG11201403572RA (hr) |
| SI (1) | SI2797917T1 (hr) |
| TW (1) | TWI562994B (hr) |
| UY (1) | UY34561A (hr) |
| WO (1) | WO2013098764A1 (hr) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| PT3176170T (pt) | 2012-06-13 | 2019-02-05 | Incyte Holdings Corp | Compostos tricíclicos substituídos como inibidores de fgfr |
| ES2916220T3 (es) | 2012-07-11 | 2022-06-29 | Blueprint Medicines Corp | Inhibidores del receptor de factor de crecimiento de fibroblasto |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| SG10201708520YA (en) | 2013-04-19 | 2017-12-28 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US9850276B2 (en) * | 2013-05-24 | 2017-12-26 | The Scripps Research Institute | Bidentate-binding modulators of LRRK2 and JNK kinases |
| ES2924111T3 (es) | 2013-10-25 | 2022-10-04 | Blueprint Medicines Corp | Inhibidores del receptor del factor de crecimiento de fibroblastos |
| US9695165B2 (en) | 2014-01-15 | 2017-07-04 | Blueprint Medicines Corporation | Inhibitors of the fibroblast growth factor receptor |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| TWI712601B (zh) | 2015-02-20 | 2020-12-11 | 美商英塞特公司 | 作為fgfr抑制劑之雙環雜環 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| CA3006897A1 (en) | 2017-08-04 | 2019-02-04 | University Health Network | Generation of oligodendrogenic neural progenitor cells |
| MA52493A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Sels d'un inhibiteur de fgfr |
| US11466004B2 (en) | 2018-05-04 | 2022-10-11 | Incyte Corporation | Solid forms of an FGFR inhibitor and processes for preparing the same |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| CA3157361A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| JP2023505258A (ja) | 2019-12-04 | 2023-02-08 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤としての三環式複素環 |
| BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| CN113651810B (zh) * | 2021-07-16 | 2023-10-13 | 上海毕得医药科技股份有限公司 | 一种3-甲酰基-1H-吡唑并[3,4-b]吡啶-5-羧酸甲酯的合成方法 |
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| PE20010306A1 (es) * | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| US20070066641A1 (en) * | 2003-12-19 | 2007-03-22 | Prabha Ibrahim | Compounds and methods for development of RET modulators |
| GB0402137D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| FR2896247B1 (fr) * | 2006-01-13 | 2008-02-29 | Sanofi Aventis Sa | Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique |
| US8129371B2 (en) * | 2007-10-16 | 2012-03-06 | Wyeth Llc | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors |
| JP2013502444A (ja) * | 2009-08-24 | 2013-01-24 | アスセピオン ファーマスーティカル、インコーポレイテッド | キナーゼ阻害剤としての５，６−ビシクロヘテロアリール含有尿素化合物 |
| FR2951172B1 (fr) * | 2009-10-13 | 2014-09-26 | Pf Medicament | Derives pyrazolopyridines en tant qu'agent anticancereux |
| BR112012018413A2 (pt) * | 2009-12-21 | 2016-08-09 | Samumed Llc | 1h-pirazol[3,4-b]piridinas e usos terapêuticos dos mesmos. |
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2011
- 2011-12-28 FR FR1162485A patent/FR2985257B1/fr active Active
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2012
- 2012-12-26 LT LTEP12824734.3T patent/LT2797917T/lt unknown
- 2012-12-26 RU RU2014131065A patent/RU2014131065A/ru not_active Application Discontinuation
- 2012-12-26 US US14/369,160 patent/US9034898B2/en active Active
- 2012-12-26 EP EP12824734.3A patent/EP2797917B1/en active Active
- 2012-12-26 CA CA2861718A patent/CA2861718C/en not_active Expired - Fee Related
- 2012-12-26 AR ARP120104965A patent/AR089452A1/es unknown
- 2012-12-26 ES ES12824734.3T patent/ES2602798T3/es active Active
- 2012-12-26 SI SI201230759A patent/SI2797917T1/sl unknown
- 2012-12-26 DK DK12824734.3T patent/DK2797917T3/en active
- 2012-12-26 HU HUE12824734A patent/HUE029515T2/en unknown
- 2012-12-26 BR BR112014015882A patent/BR112014015882A8/pt not_active Application Discontinuation
- 2012-12-26 PT PT128247343T patent/PT2797917T/pt unknown
- 2012-12-26 PL PL12824734T patent/PL2797917T3/pl unknown
- 2012-12-26 CN CN201280070640.9A patent/CN104136434B/zh active Active
- 2012-12-26 AU AU2012360095A patent/AU2012360095B2/en not_active Ceased
- 2012-12-26 MX MX2014007843A patent/MX356656B/es active IP Right Grant
- 2012-12-26 SG SG11201403572RA patent/SG11201403572RA/en unknown
- 2012-12-26 KR KR1020147019813A patent/KR20140105578A/ko not_active Application Discontinuation
- 2012-12-26 JP JP2014549609A patent/JP6049756B2/ja active Active
- 2012-12-26 WO PCT/IB2012/057727 patent/WO2013098764A1/en active Application Filing
- 2012-12-27 TW TW101150736A patent/TWI562994B/zh not_active IP Right Cessation
- 2012-12-28 UY UY0001034561A patent/UY34561A/es not_active Application Discontinuation
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2014
- 2014-06-23 IL IL233324A patent/IL233324A/en not_active IP Right Cessation
- 2014-12-02 HK HK14112113.1A patent/HK1198649A1/xx unknown
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2016
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