6715-84-0

Usage

Uses

Used in Pharmaceutical Industry:
Methyl (4-nitro-1H-pyrazol-1-yl)acetate is used as a key intermediate in the synthesis of novel substituted glycine derivatives. These derivatives have potential applications as inhibitors of Factor XIa and/or plasma kallikrein, which are important targets in the development of antithrombotic and anti-inflammatory drugs. The ability of methyl (4-nitro-1H-pyrazol-1-yl)acetate to be incorporated into complex molecular structures makes it a promising candidate for the creation of new therapeutic agents.

Upstream product

• 2075-46-9 4-nitro-1H-pyrazole 
• 96-35-5 glycolic acid methyl ester 
• 96-32-2 bromoacetic acid methyl ester 
• 96-34-4 methyl chloroacetate 

Downstream Products

• 1152853-30-9 2-(4-amino-1H-pyrazol-1-yl)-N-methylacetamide 
• 1420892-67-6 C₁₈H₂₀ClN₇O₂ 
• 1339619-68-9 N-methyl-2-(4-nitro-1H-pyrazol-1-yl)acetamide 

Relevant academic research and scientific papers

3-substituent-6-pyridine substituent-six-membered-ring-fused five-membered heterocyclic derivative as well as preparation method and application thereof

The invention discloses a 3-substituent-6-pyridine substituent-six-membered-ring-fused five-membered heterocyclic derivative as well as a preparation method and application thereof, and belongs to the technical field of medicines. The structural formula of the heterocyclic derivative is as shown in formula (I). The compound disclosed by the invention has good anti-tumor activity, can be used as a therapeutic agent for treating tumors in the field of preparation of anti-tumor drugs, and can also be used as a PI3K inhibitor.

Discovery and Early Clinical Development of an Inhibitor of 5-Lipoxygenase Activating Protein (AZD5718) for Treatment of Coronary Artery Disease

5-Lipoxygenase activating protein (FLAP) inhibitors attenuate 5-lipoxygenase pathway activity and reduce the production of proinflammatory and vasoactive leukotrienes. As such, they are hypothesized to have therapeutic benefit for the treatment of diseases that involve chronic inflammation including coronary artery disease. Herein, we disclose the medicinal chemistry discovery and the early clinical development of the FLAP inhibitor AZD5718 (12). Multiparameter optimization included securing adequate potency in human whole blood, navigation away from Ames mutagenic amine fragments while balancing metabolic stability and PK properties allowing for clinically relevant exposures after oral dosing. The superior safety profile of AZD5718 compared to earlier frontrunner compounds allowed us to perform a phase 1 clinical study in which AZD5718 demonstrated a dose dependent and greater than 90% suppression of leukotriene production over 24 h. Currently, AZD5718 is evaluated in a phase 2a study for treatment of coronary artery disease.

Design, synthesis, and biological evaluation of some novel 4-aminoquinazolines as Pan-PI3K inhibitors

A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for three PI3K isoforms with the IC50 values of picomole. The western blot assay indicated that 7b could decrease the phospho-Akt (S473) in a dose-dependent manner. Further experiments showed that 7b could induce apoptosis in MCF-7 cells. Four key hydrogen bonding interactions were found in the docking of 7b with PI3K kinase. All these results suggested that 7b is a potent PI3K inhibitor and could be considered as a potential candidate for the development of anticancer agents.

PYRROLO[2,3-B]PYRIDINE CDK9 KINASE INHIBITORS

Disclosed are compounds of Formula (IIa), wherein R1, R2, R3A, R3B, R3C, R3D, R3E, and R4 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (IIa)

HETEROCYCLYL PYRIMIDINE ANALOGUES AS JAK INHIBITORS

The present invention relates to compounds of formula (I), wherein X1 to X5, Z1 to Z3, Y0, RY1, RY2 and R have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically- mediated diseases. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.