HRP20171069T1 - Inhibitori mtor kinaze za onkološke indikacije i bolesti povezane s putom mtor/p13k/akt - Google Patents

Inhibitori mtor kinaze za onkološke indikacije i bolesti povezane s putom mtor/p13k/akt Download PDF

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HRP20171069T1
HRP20171069T1 HRP20171069TT HRP20171069T HRP20171069T1 HR P20171069 T1 HRP20171069 T1 HR P20171069T1 HR P20171069T T HRP20171069T T HR P20171069TT HR P20171069 T HRP20171069 T HR P20171069T HR P20171069 T1 HRP20171069 T1 HR P20171069T1
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Croatia
Prior art keywords
dihydropyrazino
pyrazin
pyridin
methyl
triazol
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HRP20171069TT
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Jan Elsner
Roy Harris
Branden Lee
Deborah Mortensen
Garrick K. Packard
Patrick Papa
Sophie Perrin-Ninkovic
Jennifer Riggs
Sabita Sankar
John Sapienza
Graziella I. Shevlin
Lida Tehrani
Weiming Xu
Jingjing Zhao
Jason Parnes
Loui Madakamutil
Kimberly Elizabeth Fultz
Rama K. Narla
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Signal Pharmaceuticals, Llc
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Application filed by Signal Pharmaceuticals, Llc filed Critical Signal Pharmaceuticals, Llc
Publication of HRP20171069T1 publication Critical patent/HRP20171069T1/hr

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Claims (19)

1. Spoj koji ima formulu (II): [image] ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer, naznačen time da: R1 je piridil supstituiran s jednim ili više supstituenata neovisno odabranih iz skupine koja sadrži supstituiran ili nesupstituiran C1-8 alkil, supstituiran ili nesupstituiran heterociklil, halogen, aminokarbonil, cijano, hidroksialkil, -OR, i -NR2, pri čemu svaki R je neovisno H, ili supstituiran ili nesupstituiran C1-4 alkil; R2 je supstituiran ili nesupstituiran C1-8 alkil; i R3 je H, ili supstituiran ili nesupstituiran C1-8 alkil; pri čemu izraz "supstituiran" označava supstituciju s bilo kojim od supstituenata koji su navedeni u dodatnim zahtjevima ili sa supstituentima koji su halogen; alkil; hidroksil; alkoksi; alkoksialkil; amino; alkilamino; karboksi; nitro; cijano; tiol; tioeter; imine; imid; amidin; guanidin; enamin; aminokarbonil; acilamino; fosfonato; fosfin; tiokarbonil; sulfonil; sulfon; sulfonamide; keton; aldehid; ester; urea; uretan; oksim; hidroksil amin; alkoksiamin; aralkoksiamin; N-oksid; hidrazin; hidrazid; hidrazon; azid; izocijanat; izotiocijanat; cijanat; tiocijanat; kisik (=O); B(OH)2, O(alkil)aminokarbonil; cikloalkil, koji može biti monociklički ili kondenziran ili ne-kondenziran policiklički; heterociklil, koji može biti monociklički ili kondenziran ili ne-kondenziran policiklički; monociklički ili kondenziran ili ne-kondenziran policiklički aril ili heteroaril; ariloksi; aralkiloksi; heterocikliloksi; ili heterociklil alkoksi.
2. Spoj prema zahtjevu 1, naznačen time da R2 je nesupstituirani C1-8 alkil.
3. Spoj prema zahtjevu 1, naznačen time da R3 je H.
4. Spoj prema zahtjevu 1, naznačen time da spoj je: 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-((cis-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-((trans-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-((trans-4-hidroksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-(2-metoksietil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-etil-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-((cis-4-hidroksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-izopropil-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(2-hidroksipiridin-4-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-izopropil-7-(4-metil-6-(lH-l,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(2-aminopiridin-4-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(metilamino)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-hidroksipiridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-metoksipiridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-aminopiridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-metil-7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 3-((7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-2-okso-3,4-dihidropirazino[2,3-b]pirazin-1(2H)-il)metil)benzonitril; 1-((trans-4-metoksicikloheksil)metil)-7-(4-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 3-((7-(6-(2-hidroksipropan-2-il)piridin-3-il)-2-okso-3,4-dihidropirazino[2,3-b]pirazin-1 (2H)-il)metil)benzonitril; 7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-1-(2-morfolinoetil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(2-morfolinoetil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-izopropil-7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-((cis-4-metoksicikloheksil)metil)-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-etil-7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-((trans-4-metoksicikloheksil)metil)-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-((cis-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-(2-metoksietil)-7-(4-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-(2-metoksietil)-7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-((trans-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-(ciklopentilmetil)-7-(6-(2-hidroksipropan-2-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; (S)-7-(6-(1-hidroksietil)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; (R)-7-(6-(1-hidroksietil)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-1-((tetrahidro-2H-piran-4-il)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(4-(trifluorometil)benzil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(3-(trifluorometil)benzil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(3-metoksipropil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(4-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(2-metoksietil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-((tetrahidro-2H-piran-4-il)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(2-(tetrahidro-2H-piran-4-il)etil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; 1-(1-hidroksipropan-2-il)-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on; ili 1-(2-hidroksietil)-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on, ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
5. Spoj prema zahtjevu 1, naznačen time da spoj je 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-((cis-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
6. Spoj prema zahtjevu 1, naznačen time da spoj je 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-(2-metoksietil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
7. Spoj prema zahtjevu 1, naznačen time da spoj je 7-(6-(1H-1,2,4-triazol-3-il)piridin-3-il)-1-izopropil-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
8. Spoj prema zahtjevu 1, naznačen time da spoj je 3-((7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-2-okso-3,4-dihidropirazino[2,3-b]pirazin-1(2H)-il)metil)benzonitril ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
9. Spoj prema zahtjevu 1, naznačen time da spoj je 3-((7-(6-(2-hidroksipropan-2-il)piridin-3-il)-2-okso-3,4-dihidropirazino[2,3-b]pirazin-1(2H)-il)metil)benzonitril ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
10. Spoj prema zahtjevu 1, naznačen time da spoj je 1-((cis-4-metoksicikloheksil)metil)-7-(2-metil-6-(1H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
11. Spoj prema zahtjevu 1, naznačen time da spoj je 1-etil-7-(2-metil-6-(4H-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
12. Spoj prema zahtjevu 1, naznačen time da spoj je 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-((trans-4-metoksicikloheksil)metil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
13. Spoj prema zahtjevu 1, naznačen time da spoj je 7-(6-(2-hidroksipropan-2-il)piridin-3-il)-1-(4-(trifluorometil)benzil)-3,4-dihidropirazino[2,3-b]pirazin-2(1H)-on ili njegova farmaceutski prihvatljiva sol, stereoizomer, ili njegov tautomer.
14. Farmaceutski pripravak naznačen time da sadrži učinkovitu količinu spoja prema bilo kojem od zahtjeva 1 do 13, koji je proizvoljno pogodan za oralnu, parenteralnu, mukoznu, transdermalnu ili topikalnu primjenu.
15. Spoj prema bilo kojem od zahtjeva 1 do 13 ili farmaceutski pripravak prema zahtjevu 14 naznačen time da je za uporabu u postupku liječenja ili sprječavanje raka, upalnih stanja, imunoloških stanja, neurodegenerativnih bolesti, dijabetesa, pretilosti, neuroloških poremećaja, bolesti povezanih sa starenjem ili kardiovaskularnih stanja.
16. Spoj ili farmaceutski pripravak za uporabu prema zahtjevu 15, naznačen time da rak je rak glave, vrata, oka, usta, grla, jednjaka, bronha, grkljana, ždrijela, prsnog koša, kostiju, pluća, debelog crijeva, rektuma, želuca, prostate, mokraćnog mjehura, maternice, vrata maternice, dojke, jajnika, testisa, kože, štitnjače, krvi, limfnih čvorova, bubrega, jetre, gušterače, mozga, središnjeg živčanog sustava, ili solidni tumori i tumori krvotvornih stanica; ili pri čemu upalno stanje je psorijaza, astma, alergijski rinitis, bronhitis, kronična opstruktivna plućna bolest, cistična fibroza, upalna bolest crijeva, sindrom iritabilnog crijeva, Crohnova bolest, mukozni kolitis, ulcerozni kolitis, ili pretilost; ili pri čemu imunološko stanje je reumatoidni artritis, reumatoidni spondilitis, osteoartritis, multipla skleroza, lupus, upalna bolest crijeva, ulcerativni kolitis, Crohnova bolest, miastenija gravis, Gravesova bolest, encefalomijelitis, dijabetes tipa II, dermatomiozitis, ili odbacivanje transplantata; ili pri čemu bolest povezana sa starenjem je rak, pretilost, dijabetes melitus tipa II, autoimuna bolest, kardiovaskularna bolest ili neuronska degeneracija.
17. Spoj prema bilo kojem od zahtjeva 1 do 13 ili farmaceutski pripravak prema zahtjevu 14 naznačen time da je za uporabu za inhibiciju kinaze u stanici koja eksprimira spomenutu kinazu, proizvoljno pri čemu kinaza je mTOR, DNA-PK, ili PI3K, ili njihova kombinacija.
18. In vitro postupak inhibiranja kinaze u stanici koja eksprimira navedenu kinazu, naznačen time da sadrži dovođenje u kontakt navedene stanice s učinkovitom količinom spoja prema bilo kojem od zahtjeva 1 do 13, proizvoljno pri čemu kinaza je mTOR, DNA-PK, ili PI3K, ili njihova kombinacija.
19. Spoj prema bilo kojem od zahtjeva 1 do 13 ili farmaceutski pripravak prema zahtjevu 14 naznačen time da je za uporabu u postupku liječenja ili sprječavanja stanja koja se mogu liječiti ili spriječiti inhibicijom puta kinaze, prema potrebi pri čemu put kinaze je mTOR/PI3K/Akt put; pri čemu stanje je proizvoljno multipli mijelom, limfom plaštenih stanica, difuzni limfom velikih B-stanica, akutni mijeloidni limfom, folikularni limfom, kronična limfocitna leukemija; rak dojke, pluća, endometrija, jajnika, želuca, cerviksa ili prostate; glioblastom; karcinom bubrega; hepatocelularni karcinom; karcinom debelog crijeva; neuroendokrini tumori; tumori glave i vrata; sarkomi; tumorski sindromi koji su izravno ili neizravno proizašli iz genetskih defekata u PTEN, TSC1, TSC2, NF1, AMPK, LKB1, VHL ili PKD1; Cowdenova bolest, Cowdenov sindrom, sindrom sličan Cowdenovom, sindrom Bannayan-Zonana, sindrom Bannayan-Riley-Ruvalcaba, Lhermitte-Duclos-ova bolest, karcinom endometrija, kompleks tuberozne skleroze, limfangioleiomiomatoza, neurofibromatoza 1, sindrom Peutz-Jeghers, karcinom bubrežnih stanica, Hippel-Lindau-ova bolest, Proteusov sindrom, ili policistična bolest bubrega; reumatoidni artritis; reumatoidni spondilitis; osteoartritis; giht; astma, bronhitis; alergijski rinitis; kronična opstruktivna plućna bolest; cistična fibroza; upalna bolest crijeva; sindrom iritabilnog crijeva; mukozni kolitis; ulcerativni kolitis; Crohnova bolest; Huntingtonova bolest; gastritis; ezofagitis; hepatitis; pankreatitis; nefritis; multipla skleroza; eritemski lupus; ateroskleroza; restenoza nakon angioplastike; hipertrofija lijeve klijetke; infarkt miokarda; moždani udar; ishemijska oštećenja srca, pluća, crijeva, bubrega, jetre, gušterače, slezene i mozga; akutno ili kronično odbacivanje presađivanja organa; očuvanje organa za transplantaciju; zatajenje organa ili gubitak udova; bolesti presatka protiv domaćina; endotoksinskog šoka; višestruko zatajenje organa; psorijaza; opekotine zbog izlaganja vatri, kemikalijama ili zračenju; ekcem; dermatitis; presađivanje kože; ishemija; ishemijska stanja povezana s operacijom ili traumatskom ozljedom; epilepsija; Alzheimerova bolest; Parkinsonova bolest; imunološki odgovor na bakterijske ili virusne infekcije; kaheksija; angiogene ili proliferativne bolesti.
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Families Citing this family (119)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9273077B2 (en) 2008-05-21 2016-03-01 Ariad Pharmaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
EP2300013B1 (en) 2008-05-21 2017-09-06 Ariad Pharmaceuticals, Inc. Phosphorous derivatives as kinase inhibitors
US8110578B2 (en) * 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
CA2743449C (en) 2008-11-12 2016-10-18 Ariad Pharmaceuticals, Inc. Pyrazinopyrazines and derivatives as kinase inhibitors
DE102009043260A1 (de) 2009-09-28 2011-04-28 Merck Patent Gmbh Pyridinyl-imidazolonderivate
JP2013508456A (ja) * 2009-10-26 2013-03-07 シグナル ファーマシューティカルズ， エルエルシー ヘテロアリール化合物の合成方法および精製方法
WO2011097333A1 (en) * 2010-02-03 2011-08-11 Signal Pharmaceuticals, Llc Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors
US20110275699A1 (en) * 2010-03-16 2011-11-10 University Of California Treatment For Obesity And Diabetes
US20120028972A1 (en) * 2010-07-30 2012-02-02 Lilly Wong Biomarker assays for detecting or measuring inhibition of tor kinase activity
JP5936628B2 (ja) * 2011-02-18 2016-06-22 ノバルティス・ファルマ・アクチェンゲゼルシャフトＮｏｖａｒｔｉｓ Ｐｈａｒｍａ ＡＧ ｍＴＯＲ／ＪＡＫ阻害剤併用療法
WO2012122405A2 (en) * 2011-03-08 2012-09-13 The Trustees Of Columbia University In The City Of New York Screening assays using stem cells and stem cell-derived neurons from mouse models of alzheimer's disease
JP5999177B2 (ja) 2011-05-04 2016-09-28 アリアド・ファーマシューティカルズ・インコーポレイテッド Ｅｇｆｒ発動性がんの細胞増殖阻害用化合物
US20130158023A1 (en) * 2011-08-03 2013-06-20 Signal Pharmaceuticals, Llc Identification of gene expression as a predictive biomarker for lkb1 status
AU2015200318B2 (en) * 2011-10-19 2016-10-20 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
EP3659599B1 (en) 2011-10-19 2022-12-21 Signal Pharmaceuticals, LLC 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one for use in the treatment of glioblastoma multiforme
AU2015201807B2 (en) * 2011-12-02 2016-12-08 Signal Pharmaceuticals, Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methocyclohexyl)-3,4-dihydropyrazino[2,3-b] pyrazin-2(1H)-one, a solid form thereof and methods of their use
CA3125862A1 (en) * 2011-12-02 2013-06-06 Signal Pharmaceuticals, Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
CA2862689C (en) * 2012-01-17 2020-03-10 Tyme, Inc. .alpha.-methyl-dl-tyrosine, compositions, kits, combinations and use thereof for the treatment of cancer or for reducing cell proliferation
US10646552B2 (en) 2012-01-17 2020-05-12 Tyme, Inc. Pharmaceutical compositions and methods
US10272068B2 (en) 2012-01-17 2019-04-30 Tyme, Inc. Pharmaceutical compositions and methods
US20130183263A1 (en) 2012-01-17 2013-07-18 Steven Hoffman Pharmaceutical compositions and methods
US8481498B1 (en) 2012-01-17 2013-07-09 Steven Hoffman Pharmaceutical compositions and methods
FR2986230B1 (fr) * 2012-01-30 2014-03-07 Univ Paris Diderot Paris 7 Nouveaux composes et compositions utilises comme anticancereux
US9375443B2 (en) * 2012-02-24 2016-06-28 Signal Pharmaceuticals, Llc Method for treating advanced non-small cell lung cancer (NSCLC) by administering a combination of a TOR kinase inhibitor and azacitidine or erlotinib
NZ628416A (en) 2012-03-15 2016-04-29 Signal Pharm Llc Treatment of cancer with tor kinase inhibitors
TWI664968B (zh) * 2012-03-15 2019-07-11 標誌製藥公司 使用tor激酶抑制劑之癌症治療
BR112014022700A2 (pt) * 2012-03-15 2020-06-30 Signal Pharmaceuticals, Llc uso de uma quantidade eficaz de um inibidor da quinase tor, método para melhorar o critério do grupo de trabalho 2 do antígeno prostático específico (psawg2), método para a inibição da fosforilação de s6rp, 4e-bp1 e/ou de akt, método para a inibição da atividade da proteína quinase dependente do dna (dna-pk), método para a medição da inibição da fosforilação de s6rp, 4e-bp1 ou akt, método para a medição da inibição da fosforilação de dna-pk s2056 e kit
AU2015213400B2 (en) * 2012-03-15 2017-07-27 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
MY178012A (en) 2012-03-15 2020-09-29 Signal Pharm Llc Treatment of cancer with tor kinase inhibitors
AU2015201138B2 (en) * 2012-03-15 2016-06-23 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
US20150166591A1 (en) 2012-05-05 2015-06-18 Ariad Pharmaceuticals, Inc. Methods and compositions for raf kinase mediated diseases
ES2704744T3 (es) 2012-06-13 2019-03-19 Incyte Holdings Corp Compuestos tricíclicos sustituidos como inhibidores de FGFR
AU2015213397B2 (en) * 2012-10-18 2017-07-27 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
AU2013203714B2 (en) * 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
EA039396B1 (ru) * 2012-10-18 2022-01-24 СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи Лечение рака молочной железы с тройным негативным фенотипом ингибиторами tor-киназы
AU2013202768B2 (en) * 2012-10-18 2015-11-05 Signal Pharmaceuticals, Llc Treatment of cancer with TOR kinase inhibitors
ES2638179T3 (es) 2013-01-16 2017-10-19 Signal Pharmaceuticals, Llc Compuestos de pirrolopirimidina sustituidos, composiciones de los mismos, y métodos de tratamiento con los mismos
DK2948134T3 (da) 2013-01-24 2020-06-02 Palvella Therapeutics Inc Sammensætninger til transdermal indgivelse af mtor-inhibitorer
WO2014134240A1 (en) 2013-02-28 2014-09-04 Signal Pharmaceuticals, Llc Treatment of cancer with tor kinase inhibitors
US9611283B1 (en) 2013-04-10 2017-04-04 Ariad Pharmaceuticals, Inc. Methods for inhibiting cell proliferation in ALK-driven cancers
KR102459285B1 (ko) * 2013-04-17 2022-10-27 시그날 파마소티칼 엘엘씨 1-에틸-7-(2-메틸-6-(1H-1,2,4-트리아졸-3-일)피리딘-3-일)-3,4-디하이드로피라지노[2,3-b]피라진-2(1H)-온에 관한 약학 제제, 제조방법, 고체 형태 및 사용 방법
UA119538C2 (uk) * 2013-04-17 2019-07-10 Сігнал Фармасьютікалз, Елелсі Лікування злоякісної пухлини дигідропіразинопіразинами
CN105392499B (zh) * 2013-04-17 2018-07-24 西格诺药品有限公司 用于治疗癌症的包含tor激酶抑制剂和胞苷类似物的组合疗法
US9474757B2 (en) * 2013-04-17 2016-10-25 Signal Pharmaceuticals, Llc Methods for treating cancer using TOR kinase inhibitor combination therapy
JP2016522177A (ja) * 2013-04-17 2016-07-28 シグナル ファーマシューティカルズ，エルエルシー ジヒドロピラジノ−ピラジンによる癌治療
AU2014254058B2 (en) 2013-04-17 2019-06-06 Signal Pharmaceuticals, Llc Combination therapy comprising a Dihydropyrazino-Pyrazine Compound and an androgen receptor antagonist for treating prostate cancer
TW201521725A (zh) * 2013-04-17 2015-06-16 Signal Pharm Llc 使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法
KR102221029B1 (ko) * 2013-04-17 2021-02-26 시그날 파마소티칼 엘엘씨 디하이드로피라지노-피라진을 사용한 암의 치료
US20140314752A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Methods for treating cancer using tor kinase inhibitor combination therapy
CN109776525B (zh) 2013-04-19 2022-01-21 因赛特控股公司 作为fgfr抑制剂的双环杂环
CN107474051B (zh) 2013-05-29 2020-10-30 西格诺药品有限公司 二氢吡嗪并吡嗪化合物的药物组合物、其固体形式和它们的用途
JP2016540726A (ja) 2013-10-04 2016-12-28 シグナル ファーマシューティカルズ，エルエルシー 遺伝子突然変異を特徴とする癌の予防又は治療におけるｔｏｒキナーゼ阻害剤
US10751313B2 (en) 2013-10-22 2020-08-25 Yamo Pharmaceuticals Llc Compositions and methods for treating autism
US9763903B2 (en) 2013-10-22 2017-09-19 Steven Hoffman Compositions and methods for treating intestinal hyperpermeability
US9585841B2 (en) 2013-10-22 2017-03-07 Tyme, Inc. Tyrosine derivatives and compositions comprising them
US10813901B2 (en) 2013-10-22 2020-10-27 Yamo Pharmaceuticals Llc Compositions and methods for treating autism
US9326962B2 (en) 2013-10-22 2016-05-03 Steven Hoffman Compositions and methods for treating intestinal hyperpermeability
WO2015069217A1 (en) * 2013-11-05 2015-05-14 Baylor College Of Medicine Src kinase inhibition as treatment for lympangioleiomyomatosis and tuberous sclerosis
NZ714742A (en) * 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
WO2015160880A1 (en) 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
US20150297605A1 (en) * 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc Methods for treating cancer using tor kinase inhibitor combination therapy
WO2015160882A1 (en) 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc SOLID FORMS COMPRISING 7-(6-(2-HYDROXYPROPAN-2YL) PYRIDIN-3-YL)-1-(TRANS)-4-METHOXYCYCLOHEXYL)-3, 4-DIHYDROPYRAZINO[2,3-b] PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
JP2017514806A (ja) * 2014-04-16 2017-06-08 シグナル ファーマシューティカルズ，エルエルシー Ｔｏｒキナーゼ阻害剤組み合わせ療法を使用して癌を治療する方法
NZ629796A (en) 2014-07-14 2015-12-24 Signal Pharm Llc Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
KR20170024120A (ko) 2014-07-14 2017-03-06 시그날 파마소티칼 엘엘씨 치환된 피롤로피리미딘 화합물을 사용한 암의 치료방법, 이의 조성물
CN107073066B (zh) 2014-09-11 2021-09-17 加利福尼亚大学董事会 mTORC1抑制剂
US9987241B2 (en) 2014-09-25 2018-06-05 The Board Of Regents Of The University Of Oklahoma Enzyme conjugate and prodrug cancer therapy
US10851105B2 (en) 2014-10-22 2020-12-01 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
AU2016219822B2 (en) 2015-02-20 2020-07-09 Incyte Holdings Corporation Bicyclic heterocycles as FGFR inhibitors
US10722484B2 (en) 2016-03-09 2020-07-28 K-Gen, Inc. Methods of cancer treatment
US10159665B2 (en) 2016-03-23 2018-12-25 Louis Habash Preventing amyloid plaque formation by treating a human subject with a nitroxide
US10231959B2 (en) 2016-03-23 2019-03-19 Louis Habash Increasing expression level of apoptosis-related genes by treating a human subject with a nitroxide
US20180078539A1 (en) 2016-03-23 2018-03-22 Louis Habash T-cell regulation in t-cell mediated diseases by reducing pathogenic function of th17 in a human subject through treatment with a nitroxide
CA3056059C (en) * 2016-03-23 2023-02-14 Louis Habash Increasing expression level of apoptosis-related genes by treating a human subject with a nitroxide
US10818331B2 (en) 2016-09-27 2020-10-27 Spin Memory, Inc. Multi-chip module for MRAM devices with levels of dynamic redundancy registers
JP7108631B2 (ja) 2017-01-06 2022-07-28 パルヴェラ セラピューティクス、インク． ｍＴＯＲ阻害剤の無水組成物およびその使用方法
WO2018183868A1 (en) * 2017-03-31 2018-10-04 Bioventures, Llc Inhibitors of dna pk and uses thereof
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
IL271491B2 (en) 2017-06-22 2023-09-01 Celgene Corp Treatment of carcinoma of the liver characterized by hepatitis b virus infection
WO2020032951A1 (en) 2018-08-09 2020-02-13 The Board Of Regents Of The University Of Oklahoma Antimalarial enzyme conjugates, kits containing same, and methods of producing and using same
KR102133794B1 (ko) * 2017-08-24 2020-07-15 주식회사 셀투인 세포 소기관 내 글루타치온 측정용 실시간 형광 이미징 센서 및 이의 제조 방법
US10656994B2 (en) 2017-10-24 2020-05-19 Spin Memory, Inc. Over-voltage write operation of tunnel magnet-resistance (“TMR”) memory device and correcting failure bits therefrom by using on-the-fly bit failure detection and bit redundancy remapping techniques
AU2018360801A1 (en) 2017-11-01 2020-05-14 Celgene Corporation Process for producing a T cell composition
KR102083916B1 (ko) 2017-11-23 2020-03-03 서울대학교산학협력단 대장암 진단을 위한 ｔｃｆ７ 돌연변이의 용도 및 게다토리십 약물내성을 갖는 대장암 치료용 조성물
SG11202004231YA (en) * 2017-12-04 2020-06-29 BIAL PORTELA & Cª S A Dopamine-β-hydroxylase inhibitors
US10886330B2 (en) 2017-12-29 2021-01-05 Spin Memory, Inc. Memory device having overlapping magnetic tunnel junctions in compliance with a reference pitch
US10840439B2 (en) 2017-12-29 2020-11-17 Spin Memory, Inc. Magnetic tunnel junction (MTJ) fabrication methods and systems
US10596165B2 (en) 2018-02-12 2020-03-24 resTORbio, Inc. Combination therapies
IL312291A (en) 2018-05-01 2024-06-01 Revolution Medicines Inc C-26-linked rapamycin analogs as MTOR inhibitors
LT3788049T (lt) 2018-05-01 2023-07-25 Revolution Medicines, Inc. Rapamicino analogai, sujungti su c40-, c28- ir c32-, kaip mtor inhibitoriai
BR112020022392A2 (pt) 2018-05-04 2021-02-02 Incyte Corporation formas sólidas de um inibidor de fgfr e processos para preparação das mesmas
MX2020011639A (es) 2018-05-04 2021-02-15 Incyte Corp Sales de un inhibidor de receptores de factor de crecimiento de fibroblastos (fgfr).
US10411185B1 (en) 2018-05-30 2019-09-10 Spin Memory, Inc. Process for creating a high density magnetic tunnel junction array test platform
DK3813946T3 (da) 2018-06-15 2024-08-19 Janssen Pharmaceutica Nv Rapamycin-analoger og anvendelser deraf
JP2021530463A (ja) 2018-07-02 2021-11-11 パルヴェラ セラピューティクス、インク． ｍＴＯＲ阻害剤の無水組成物および使用方法
US10650875B2 (en) 2018-08-21 2020-05-12 Spin Memory, Inc. System for a wide temperature range nonvolatile memory
JP2022500384A (ja) 2018-09-10 2022-01-04 ミラティ セラピューティクス， インコーポレイテッド 組み合わせ療法
US10971680B2 (en) 2018-10-01 2021-04-06 Spin Memory, Inc. Multi terminal device stack formation methods
US11621293B2 (en) 2018-10-01 2023-04-04 Integrated Silicon Solution, (Cayman) Inc. Multi terminal device stack systems and methods
WO2020185532A1 (en) 2019-03-08 2020-09-17 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
UY38806A (es) 2019-08-01 2021-02-26 Novartis Ag Compuestos inhibidores tricíclicos de kars dependientes de akr1c3, composiciones y sus usos
IL291901A (en) 2019-10-14 2022-06-01 Incyte Corp Bicyclyl heterocycles as fgr suppressors
WO2021076728A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
KR20220131900A (ko) 2019-12-04 2022-09-29 인사이트 코포레이션 Fgfr 억제제의 유도체
WO2021113479A1 (en) 2019-12-04 2021-06-10 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
JP2023506410A (ja) 2019-12-05 2023-02-16 アナクリア セラピューティクス， インコーポレイテッド ラパマイシン類似体及びその使用
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021219090A1 (zh) * 2020-04-29 2021-11-04 北京泰德制药股份有限公司 喹喔啉二酮衍生物作为kras g12c突变蛋白的不可逆抑制剂
CN115916350A (zh) * 2020-07-22 2023-04-04 南京正大天晴制药有限公司 Akt抑制剂的单位剂量组合物
WO2022166866A1 (zh) * 2021-02-08 2022-08-11 南京明德新药研发有限公司 二氢吡嗪并吡嗪类大环化合物
JP2024506381A (ja) 2021-02-16 2024-02-13 ヴァクシテック ノース アメリカ， インコーポレイテッド 両親媒性ペプチドに基づく自己集合ナノ粒子
CA3215903A1 (en) 2021-04-12 2022-10-20 Incyte Corporation Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent
EP4352059A1 (en) 2021-06-09 2024-04-17 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
WO2022266251A1 (en) * 2021-06-16 2022-12-22 The Board Of Trustees Of The Leland Stanford Junior University Compositions for treatment of psoriasis
WO2023170107A1 (en) 2022-03-07 2023-09-14 Centre Hospitalier Universitaire Vaudois (Chuv) Pi3k/akt/mtor inhibitor for improving the cellular uptake of a radiopharmaceutical
WO2024092030A1 (en) 2022-10-25 2024-05-02 Vaccitech North America, Inc. Self-assembling nanoparticles
WO2024165859A1 (en) 2023-02-07 2024-08-15 Quell Therapeutics Limited Culture method for treg cells

Family Cites Families (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE262026C (hr)
US3507866A (en) 1967-08-08 1970-04-21 Merck & Co Inc 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation
US3567725A (en) 1968-11-20 1971-03-02 Merck & Co Inc Process for preparation of 1h-imidazo-(4,5-b)pyrazin-2-ones
US4294836A (en) 1980-03-24 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]-pyridine-2-thiones and their cardiotonic use
US4317909A (en) 1980-03-24 1982-03-02 Sterling Drug Inc. Preparation of 1,3-dihydro-5-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones
US4294837A (en) 1980-03-28 1981-10-13 Sterling Drug Inc. 1,3-Dihydro-6-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones and -imidazo[4,5-b]pyridine-2-thiones and their cardiotonic use
US4309537A (en) 1980-03-28 1982-01-05 Sterling Drug Inc. Production of imidazo[4,5-b]pyridin-2-ones or thiones
GB8709448D0 (en) 1987-04-21 1987-05-28 Pfizer Ltd Heterobicyclic quinoline derivatives
JPS63275582A (ja) 1987-05-02 1988-11-14 Naade Kenkyusho:Kk ２−アミノイミダゾ〔４，５−ｂ〕ピリジン誘導体の製造方法
DD262026A1 (de) 1987-07-10 1988-11-16 Akad Wissenschaften Ddr Verfahren zur herstellung von 4-substituierten 6-(pyrid-4-yl)-2,4-dihydro-1h-imidazo[4,5-b]pyrid-2-onen
FR2643903A1 (fr) 1989-03-03 1990-09-07 Union Pharma Scient Appl Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux
US4963561A (en) 1990-02-28 1990-10-16 Sterling Drug Inc. Imidazopyridines, their preparation and use
TW274550B (hr) 1992-09-26 1996-04-21 Hoechst Ag
WO1995003009A1 (en) 1993-07-22 1995-02-02 Oculex Pharmaceuticals, Inc. Method of treatment of macular degeneration
WO1995003807A1 (en) 1993-07-27 1995-02-09 The University Of Sydney Treatment of age-related macular degeneration
MX9702245A (es) * 1994-11-14 1997-06-28 Warner Lambert Co Seis-aril-pirido(2,3-d)pirimidinas y naftiridinas para inhibir la proliferacion celular mediada por la proteina cinasa tirosina.
IT1274549B (it) 1995-05-23 1997-07-17 Indena Spa Uso di flavanolignani per la preparazione di medicamenti ad attivita' antiproliferativa nei tumori dell'utero,dell'ovaio e del seno
DE19601627A1 (de) 1996-01-18 1997-07-24 Bayer Ag Heteroatomhaltige Cyclopentanopyridyl-Oxazolidinone
US5800819A (en) 1996-01-25 1998-09-01 National Institute For Pharmaceutical Research And Development Federal Ministry Of Science And Technology Piper guineense, pterocarpus osun, eugenia caryophyllata, and sorghum bicolor extracts for treating sickle cell disease
US6281230B1 (en) 1996-07-24 2001-08-28 Celgene Corporation Isoindolines, method of use, and pharmaceutical compositions
US5635517B1 (en) 1996-07-24 1999-06-29 Celgene Corp Method of reducing TNFalpha levels with amino substituted 2-(2,6-dioxopiperidin-3-YL)-1-oxo-and 1,3-dioxoisoindolines
US6093728A (en) 1997-09-26 2000-07-25 Asta Medica Aktiengesellschaft Methods of modulating serine/threonine protein kinase function with azabenzimidazole-based compounds
ZA9810490B (en) 1997-12-03 1999-05-20 Dainippon Pharmaceutical Co 2-Aryl-8-oxodihydropurine derivative process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor
US6015803A (en) 1998-05-04 2000-01-18 Wirostko; Emil Antibiotic treatment of age-related macular degeneration
US6225348B1 (en) 1998-08-20 2001-05-01 Alfred W. Paulsen Method of treating macular degeneration with a prostaglandin derivative
US6001368A (en) 1998-09-03 1999-12-14 Protein Technologies International, Inc. Method for inhibiting or reducing the risk of macular degeneration
JP2003146987A (ja) 1999-05-31 2003-05-21 Dainippon Pharmaceut Co Ltd ２−アリールプリン−９−アセトアミド誘導体
JP3814125B2 (ja) 1999-06-02 2006-08-23 大日本住友製薬株式会社 ２−アリール−８−オキソジヒドロプリン誘導体からなる医薬
CA2398163C (en) * 2000-01-24 2011-02-22 Kinacia Pty Ltd. Therapeutic morpholino-substituted compounds
JP2002167387A (ja) 2000-11-29 2002-06-11 Dainippon Pharmaceut Co Ltd ２−（７，８−ジヒドロ−８−オキソ−９ｈ−プリン−９−イル）酢酸誘導体
EP1347982B1 (en) 2000-12-12 2005-11-16 Neurogen Corporation Spiro isobenzofuran-1,4'-piperidin]-3-ones and 3h-spiroisobenzofuran-1,4'-piperidines
AU2002257217A1 (en) 2001-04-24 2002-11-05 Broadcom Corporation Alerting system, architecture and circuitry
JP3876254B2 (ja) 2001-09-04 2007-01-31 ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト 新規なジヒドロプテリジノン、その製造方法及びその医薬組成物としての使用
EP1438048A1 (en) 2001-10-18 2004-07-21 Boehringer Ingelheim Pharmaceuticals Inc. 1,4-disubstituted benzo-fused urea compounds as cytokine inhibitors
US7968569B2 (en) 2002-05-17 2011-06-28 Celgene Corporation Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
US20040204420A1 (en) 2002-08-05 2004-10-14 Rana Tariq M. Compounds for modulating RNA interference
US7189740B2 (en) 2002-10-15 2007-03-13 Celgene Corporation Methods of using 3-(4-amino-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myelodysplastic syndromes
US20040091455A1 (en) 2002-10-31 2004-05-13 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for treatment and management of macular degeneration
US7563810B2 (en) 2002-11-06 2009-07-21 Celgene Corporation Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases
BRPI0406809A (pt) 2003-01-17 2005-12-27 Warner Lambert Co Heterociclos substituìdos de 2-aminopiridina como inibidores da proliferação celular
CA2517020C (en) 2003-02-26 2012-06-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, method for the production and use thereof in the form of drugs
GB2400101A (en) 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
US20050100529A1 (en) 2003-11-06 2005-05-12 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of asbestos-related diseases and disorders
CN1882347A (zh) * 2003-11-21 2006-12-20 阿雷生物药品公司 Akt蛋白激酶抑制剂
AU2005226649B2 (en) 2004-03-22 2010-04-29 Celgene Corporation Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of skin diseases or disorders
EP1734951A2 (en) * 2004-04-08 2006-12-27 TopoTarget A/S Diphenyl-indol-2-on compounds and their use in the treatment of cancer
MXPA06012278A (es) 2004-04-23 2007-01-31 Celgene Corp Metodos de uso y composiciones que comprenden compuestos inmunomoduladores para el tratamiento y manejo de la hipertension pulmonar.
CN101123968A (zh) 2004-06-04 2008-02-13 艾科斯有限公司 肥大细胞病的治疗方法
DE102004029784A1 (de) 2004-06-21 2006-01-05 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel
WO2006001266A1 (ja) 2004-06-23 2006-01-05 Banyu Pharmaceutical Co., Ltd. ２－アリールプリン誘導体の製造方法
WO2006020755A2 (en) 2004-08-10 2006-02-23 Beth Israel Deaconess Medical Center, Inc. Methods for identifying inhibitors of the mtor pathway as diabetes therapeutics
GB0420719D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
EP1796467A4 (en) 2004-09-24 2009-07-01 Janssen Pharmaceutica Nv INHIBITORS IMIDAZO {4,5-B} PYRAZINONE PROTEIN KINASES
MX2007005159A (es) 2004-10-29 2007-06-26 Tibotec Pharm Ltd Derivados de pirimidina biciclicos inhibidores del vih.
AU2005304420A1 (en) 2004-11-12 2006-05-18 Celgene Corporation Methods and compositions using immunomodulatory compounds for treatment and management of parasitic diseases
CA2588597A1 (en) 2004-11-23 2006-06-01 Celgene Corporation Methods and compositions using immunomodulatory compounds for treatment and management of central nervous system injury
ZA200704964B (en) 2004-12-01 2008-10-29 Celgene Corp Methods and compositions using immunomodulatory compounds for the treatment of immunodeficiency disorders
AU2005316668B2 (en) 2004-12-13 2012-09-06 Millennium Pharmaceuticals, Inc. Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors
WO2006091737A1 (en) 2005-02-24 2006-08-31 Kemia, Inc. Modulators of gsk-3 activity
WO2006090169A1 (en) * 2005-02-25 2006-08-31 Kudos Pharmaceuticals Limited 2,4-diamino-pyridopyrimidine derivatives and their use as mtor inhibitors
EP1874772A1 (en) 2005-04-05 2008-01-09 Pharmacopeia, Inc. Purine and imidazopyridine derivatives for immunosuppression
SI1951724T1 (sl) * 2005-11-17 2011-09-30 Osi Pharmaceuticals Llc Kondenzirani biciklični mTOR inhibitorji
EP2995619B1 (en) 2006-08-02 2019-09-25 Cytokinetics, Inc. Certain chemical entities comprising imidazopyrimidines, compositions and methods
ZA200902382B (en) 2006-10-19 2010-08-25 Signal Pharm Llc Heteroaryl compounds, compositions thereof, and their use as protein kinase inhibitors
MX2009009304A (es) 2007-03-01 2009-11-18 Novartis Ag Inhibidores de cinasa pim y metodos para su uso.
US8110578B2 (en) 2008-10-27 2012-02-07 Signal Pharmaceuticals, Llc Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway
JP2013508456A (ja) * 2009-10-26 2013-03-07 シグナル ファーマシューティカルズ， エルエルシー ヘテロアリール化合物の合成方法および精製方法

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