761440-91-9

Basic information

• Product Name: Benzenamine, 2-methoxy-4-[4-(4-morpholinyl)-1-piperidinyl]-
• Synonyms: D-1273
• CAS NO: 761440-91-9
• Molecular Formula: C16H25N3O2
• Molecular Weight: 291.393
• Mol File: 761440-91-9.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 480.2±45.0 °C(Predicted)
• Density: 1.164±0.06 g/cm3(Predicted)
• CAS DataBase Reference: Benzenamine, 2-methoxy-4-[4-(4-morpholinyl)-1-piperidinyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzenamine, 2-methoxy-4-[4-(4-morpholinyl)-1-piperidinyl]-(761440-91-9)
• EPA Substance Registry System: Benzenamine, 2-methoxy-4-[4-(4-morpholinyl)-1-piperidinyl]-(761440-91-9)

Safety Data

• Hazardous Substances Data: 761440-91-9(Hazardous Substances Data)

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

• 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 
• 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 
• 1395171-89-7 C₃₂H₄₆N₈O₃ 

Relevant articles and documents

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.

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.

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.