761440-87-3

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-amino-3-methoxyphenyl)piperidin-4-ol is used as a pharmaceutical compound for its potential therapeutic applications. The presence of piperidine and phenol moieties in its structure suggests that it may be utilized in the development of drugs targeting various medical conditions. Its specific application and efficacy would need to be determined through further research and clinical trials.

Upstream product

• 761440-22-6 1-(3-methoxy-4-nitrophenyl)piperidin-4-ol 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 5382-16-1 4-HYDROXYPIPERIDINE 

Downstream Products

• 1234480-53-5 5-ethyl-2-((4-(4-hydroxypiperidin-1-yl)-2-methoxyphenyl)-amino)-11-methyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one 
• 1254783-16-8 C₂₅H₂₆ClN₅O₄ 

Relevant academic research and scientific papers

Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold

Recent reports have highlighted the dual bromodomains of TAF1 (TAF1(1,2)) as synergistic with BET inhibition in cellular cancer models, engendering interest in TAF/BET polypharmacology. Here, we examine structure activity relationships within the BI-2536 PLK1 kinase inhibitor scaffold, previously reported to bind BRD4. We examine binding by this ligand to TAF1(2) and apply structure guided design strategies to discriminate binding to both the PLK1 kinase and BRD4(1) bromodomain while retaining activity on TAF1(2). Through this effort we discover potent dual inhibitors of TAF1(2)/BRD4(1), as well as biased derivatives showing marked TAF1 selectivity. We resolve X-ray crystallographic data sets to examine the mechanisms of the observed TAF1 selectivity and to provide a resource for further development of this scaffold.

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.

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.

Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors

To search for potent nitric oxide (NO) donating epidermal growth factor receptor (EGFR) inhibitors, a series of phenylsulfonylfuroxan-based anilinopyrimidines 10a-h were synthesized and biologically evaluated. Compounds 10f-h exhibited potent inhibitory activity against EGFR L858R/T790M and were as potent as WZ4002 in inhibition of H1975 cells harboring EGFR L858R/T790M. Additionally, 10h produced high levels of NO in H1975 cells but not in normal human cells, and its antiproliferative activity was diminished by hemoglobin, an NO scavenger. Furthermore, 10h inhibited EGFR activation and downstream signaling in H1975 cells. These results suggest that the strong antiproliferative activity of 10h could be attributed to the synergic effects of high levels of NO production and inhibition of EGFR and downstream signaling in the cancer cells.

NOVEL COMPOUNDS 515

There is provided novel pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy

2- [ (2-{PHENYLAMINO}-1H-PYRROLO [2, 3-D] PYRIMIDIN-4-YL) AMINO] BENZAMIDE DERIVATIVES AS IGF-1R INHIBITORS FOR THE TREATMENT OF CANCER

Novel pyrrolopyrimidines as shown in formula (I) and pharmaceutically acceptable derivatives thereof. The compounds are useful in the inhibition of IGF-1R.

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.