761440-91-9

Upstream product

• 125541-20-0 tert-butyl 4-(morpholin-4-yl)piperidine-1-carboxylate 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 446-36-6 5-fluoro-2-nitrophenol 
• 53617-35-9 4-(piperidin-4-yl)morpholine 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 761440-35-1 4-(1-(3-methoxy-4-nitrophenyl)piperidin-4-yl)morpholine 

Downstream Products

• 1089279-26-4 N-(2,6-difluorophenyl)-3-{3-[2-({2-(methyloxy)-4-[4-(4-morpholinyl)-1-piperidinyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide 
• 1232399-14-2 [2-methoxy-4-(4-(morpholin-4-yl)-piperidin-1-yl)-phenyl]-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-amine 
• 1395171-89-7 C₃₂H₄₆N₈O₃ 

Relevant academic research and scientific papers

Discovery and structure ? activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors

Internal tandem duplications of FLT3 (FLT3-ITD) occur in approximately 25% of all acute myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially, compounds 17 and 19 inhibited the quizartinib resistance- conferring mutations, FLT3D835Y, both with IC50 values of 0.3 nM. Moreover, western blot analysis indicated that compounds 17 and 19 potently inhibited the phosphorylation of FLT3 and attenuated downstream signaling in AML cells. These results indicated that pyrazolo[1,5-a]pyrimidine derivatives could be promising FLT3-ITD inhibitors for the treatment AML.

PYRIMIDINE DERIVATIVE AND USE THEREOF

The present invention provides a pyrimidine derivative and a use thereof. The pyrimidine derivative is the compound shown in formula I or a pharmaceutically acceptable salt, hydrate, solvate, metabolite or prodrug thereof, wherein, R1, R2, R3, R4 and R5 are, for example, as defined in the specification. The compound can act as an ALK inhibitor, and is for preparing an anti-tumor medicament for suppressing an anaplastic lymphoma kinase.

HETEROCYCLIC COMPOUND

The present invention provides a compound having a CaMKII inhibitory action, which is expected to be useful as an agent for the prophylaxis or treatment of cardiac diseases (particularly catecholaminergic polymorphic ventricular tachycardia, postoperative atrial fibrillation, heart failure, fatal arrhythmia) and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

Tyrosine Kinase Inhibitor And Uses Thereof

Disclosed is a compound of Formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, or their stereoisomers, which can be used as tyrosine kinase inhibitor. Also disclosed is a method for preparing the compound, a pharmaceutical composition and a kit comprising the compound, and uses of the compound. The compound can be used as tyrosine kinase inhibitor, or can be used to reduce or inhibit activity of EGFR or mutant thereof, such as EGFR mutant comprising T790M mutation, in a cell, or to treat and/or prevent a disease associated with overactivity of EGFR, such as cancer.

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase

In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

INHIBITOR COMPOUNDS

The present invention relates to compounds of formula (I), wherein R, R, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1 - also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them

PYRROLOTRIAZINES AS ALK AND JAK2 INHIBITORS

The present invention provides a compound of formula (I) or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula (I) has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.

Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimi

Imidazopyridine Kinase Inhibitors

The present invention provides imidazopyridine compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.

2, 4- DI (PHENYLAMINO) PYRIMIDINES USEFUL IN THE TREATMENT OF NEOPLASTIC DISEASES, INFLAMMATORY AND IMMUNE SYSTEM DISORDERS

Novel pyrimidine derivatives of formula (I), to processes for their production, their use as pharmaceuticals in the treatment of neoplastic diseases, inflammatory and immune system disorders and to pharmaceutical compositions comprising them.