385382-48-9

Usage

Uses

5-Bromo-N-cyclopropylnicotinamide can be used to prepare antibacterial drugs.

Upstream product

• 20826-04-4 5-bromo-3-pyridinecarboxylic acid 
• 765-30-0 Cyclopropylamine 
• 39620-02-5 5-bromonicotinoyl chloride 

Downstream Products

• 638219-62-2 5-bromo-N-cyclopropyl-1-oxy-nicotinamide 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of novel Bcr-AblT315I inhibitors incorporating amino acids as flexible linker

Despite the success of imatinib in CML therapy through Bcr-Abl inhibition, acquired drug resistance occurs over time in patients. In particular, the resistance caused by T315I mutation remains a challenge in clinic. Herein, we embarked on a structural optimization campaign aiming at discovery of novel Bcr-Abl inhibitors toward T315I mutant based on previously reported dibenzoylpiperazin derivatives. We proposed that incorporation of flexible linker could achieve potent inhibition of Bcr-AblT315I by avoiding steric clash with bulky sidechain of Ile315. A library of 28 compounds with amino acids as linker has been developed and evaluated. Among them, compound AA2 displayed the most potent activity against Bcr-AblWT and Bcr-AblT315I, as well as toward Bcr-Abl driven K562 and K562R cells. Further investigations indicated that AA2 could induce apoptosis of K562 cells and down regulate phosphorylation of Bcr-Abl. In summary, the compounds with amino acid as novel flexible linker exhibited certain antitumor activities, providing valuable hints for the discovery of novel Bcr-Abl inhibitors to overcome T315I mutant resistance, and AA2 could be considered as a candidate for further optimization.

Hydroxyproline peptoid derivative and preparation method and application thereof

Disclosed are a hydroxyproline peptoid derivative and a preparation method and application thereof. With biphenyl pyridine as a hinge region binding fragment, by adopting a design strategy of a fragment drug and introducing L-hydroxyproline as a flexible Linker, a peptoid micromolecule-like compound library with kinase inhibition activity is constructed, and through screening of ADP-Glo and otheractivity tests, a peptoid tyrosine-like kinase inhibitor which has Bcr-Abl kinase inhibition activity and prevents the proliferation of tumor cells is found. The compound can be used for preparing anti-tumor drugs and has the activity of inhibiting Bcr-Abl and Bcr-AblT315I kinases and activity of inhibiting the cell proliferation of K562 cells. By introducing the L-hydroxyproline, the structural diversity of the Bcr-Abl inhibitor is expanded, the activity result shows that the introduction of proline has a certain effect on the inhibition activity of the compound, and the proline can serve asa novel pharmacological-effect fragment of the Bcr-Abl tyrosine kinase inhibitor.

A containing tert-Leu [...] compound and its preparation method and application (by machine translation)

A containing tert-Leu [...] compound and its preparation method and application, the use of acylated, Suzuki coupling, condensation of the reaction to synthesize the target compound, and construct the compound library, the compound has the molecular structure of the Bcr - Abl small molecule tyrosine kinase inhibitor, this invention adopts the fragment-based drug design strategy, to biphenyl pyridine is hinge-binding fragment, is introduced into the L - tert-leucine is a flexible Linker, to construct a kinase-inhibiting activity of a small molecule compound library [...], and through the ADP - Glo screening it has been found that the kinase activity of Bcr - Abl kinase-inhibiting activity of a tyrosine kinase inhibitor. Kinase screening test indicates that this compound to the Abl kinase, T315I mutation Abl kinase has a certain inhibition activity, cell proliferation experiment shows that most of the compound to the K562 cells with certain inhibiting activity. (by machine translation)

Tert-butyl-substituted serine-containing peptoid compound and preparation and application methods thereof

Disclosed are a tert-butyl-substituted serine-containing peptoid compound and preparation and application methods thereof. As a target compound, the tert-butyl-substituted serine-containing peptoid compound is synthesized via reactions such as acylation,

Alanine derivative and preparation method and application thereof

The invention discloses an alanine derivative and a preparation method and application thereof. The preparation comprises the following steps: taking biphenylpyridine as a hinge region binding fragment, introducing L-alanine as a flexible linker by adopting a fragment drug design strategy to construct a compound library with kinase inhibitory activity, and discovering a tyrosine kinase inhibitor with Bcr-Abl kinase inhibitory activity through ADP-Glo kinase activity screening. The compound can be used for preparing anti-tumor (chronic myelogenous leukemia) drugs, inhibits kinase activity of Bcr-Abl and Bcr-AblT315I, and has the activity of inhibiting cell proliferation of K562 cells. The introduction of an alanine structure has an important effect on the inhibitory activity of the compound, the structural diversity of the kinase inhibitor can be expanded, and the activity result shows that the structure can be used as a Linker pharmacodynamic fragment of the Bcr-Abl tyrosine kinase inhibitor.

Alanine-containing peptoid compounds and preparation method and application thereof

The invention discloses alanine-containing peptoid compounds and a preparation method and application thereof. By adoption of a fragment based drug design strategy, biphenyl pyridine serves as a hingeregion binding fragment, L-alanine is introduced as fle

Compound containing hydroxyproline and preparation method and application of compound

The invention discloses a compound containing hydroxyproline and a preparation method and application of the compound. Biphenyl pyridine serves as a hinge area bonded group, a design strategy of fragment drugs is adopted, L-hydroxyproline is introduced as

Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker

Forty-two compounds (series 8, 9 and 10) incorporated with diacylated piperazine have been synthesized and evaluated as novel Bcr-Abl inhibitors based on 'six-atom linker'. Five of them, 8d, 8h, 8l, 10m and 10p, displayed potent Bcr-Abl inhibitory activity comparable with Imatinib. Moreover, compounds 8e, 10q, 10s, and 10u were potent Bcr-Abl inhibitors with IC50 values at the sub-micromolecular level. Most compounds exhibited moderate to high antiproliferative activity against K562 cells. In particular, compound 9e was the most promising Bcr-Abl inhibitor. Docking studies revealed that the binding modes of these compounds were similar with Imatinib. These compounds could be considered as promising lead compounds for further optimization.

Design, synthesis, and biological evaluation of 8-biarylquinolines: A novel class of PDE4 inhibitors

The structure-activity relationship of a novel series of 8-biarylquinolines acting as type 4 phosphodiesterase (PDE4) inhibitors is described herein. Prototypical compounds from this series are potent and non-selective inhibitors of the four distinct PDE4 (IC50 50 0.5 μM) the LPS-induced release of the cytokine TNF-α. Optimized inhibitors were evaluated in vivo for efficacy in an ovalbumin-induced bronchoconstriction model in conscious guinea pigs. Their propensity to produce an emetic response was evaluated by performing pharmacokinetic studies in squirrel monkeys. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of efficacy over emesis.

8-(BIARYL) QUINOLINE PDE4 INHIBITORS

8-(biaryl) quinolines wherein the bi-aryl group at the 8-position is in a meta relationship to the quinoline group, are PDE4 inhibitors useful in the treatment of asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic granuloma, psoriasis and other benign or malignant proliferative skin diseases, endotoxic shock, laminitis in horses, colic in horses, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, inflammatory arthritis, chronic glomerulonephritis, atopic dermatitis, urticaria, adult respiratory distress syndrome, chronic obstructive pulmonary disease in animals, diabetes insipidus, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, arterial restenosis, ortherosclerosis, atherosclerosis, neurogenic inflammation, pain, cough, rheumatoid arthritis, ankylosing spondylitis, transplant rejection, graft versus host disease, hypersecretion of gastric acid, bacterial, fungal induced sepsis, viral induced sepsis, fungal induced septic shock, viral induced septic shock, inflammation-mediated chronic tissue degeneration, cytokine-mediated chronic tissue degeneration, osteoarthritis, cancer, cachexia, muscle wasting, depression, memory impairment, tumour growth, or cancerous invasion of normal tissues.In another aspect, the present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and cognition enhancing amount of a phosphodiesterase-4 inhibitor.