124403-90-3

Upstream product

• 78-83-1 2-methyl-propan-1-ol 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 99-96-7 4-hydroxy-benzoic acid 
• 513-36-0 isobutyryl chloride 
• 78-77-3 Isobutyl bromide 
• 513-38-2 Isobutyl iodide 

Downstream Products

• 30762-00-6 4-isobutoxybenzoic acid 
• 1373823-20-1 4-(2-methylpropoxy)-N-[8-methyl-3-(pyrrolidin-1-ylmethyl)-quinolin-7-yl]benzamide 
• 40782-45-4 4-(2-methylpropoxy)benzoyl chloride 
• 706779-91-1 N-(1-methylpiperidin-4-yl)-N-(4-fluorophenylmethyl)-N′-(4-(2-methylpropyloxyl)phenylmethyl)carbamide 
• 1030513-44-0 4-isobutoxybenzamide 
• 4734-09-2 1-[4-(2-methylpropyloxy)phenyl]methanamine 
• 91430-26-1 4-Isobutyloxy-benzoesaeurehydrazid 

Relevant academic research and scientific papers

Identification of new aryl hydrocarbon receptor (AhR) antagonists using a zebrafish model

A new series of 1,3-diketone, heterocyclic and α,β-unsaturated derivatives were synthesized and evaluated for their AhR antagonist activity using zebrafish and mammalian cells. Compounds 1b, 2c, 3b and 5b showed significant AhR antagonist activity in a transgenic zebrafish model. Among them, compound 3b, and 5b were found to have excellent AhR antagonist activity with IC50 of 3.36 nM and 8.3 nM in a luciferase reporter gene assay. In stem cell proliferation assay, compound 5b elicited marked HSC expansion.

Synthesis, Antiproliferative and Antioxidant Activity of 3-Mercapto-1,2,4-Triazole Derivatives as Combretastatin A-4 Analogues

Two series of 3-mercapto-1,2,4-triazole derivatives containing alkoxy substituents different in size and position were synthesized and their structures were characterized by FT-IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. The synthesized compounds were assessed for their antiproliferative activity against colon cancer cell line (SW480). The results indicated that the size and position of the alkoxy group significantly influenced the antiproliferative activity. The highest cancer cell growth inhibition values were observed for the compounds containing 3,4,5-trimethoxyphenyl groups in their structures (57.74, 54.14 and 60.70% at 50 μM for compounds 5a, 12b and 14, respectively). The synthesized compounds were also subjected to DPPH protocol for evaluating the antioxidant activity. The results showed that all compounds had moderate to high levels of antioxidant capacity as compared to ascorbic acid as standard, the highest free radical scavenging capacity of 75% was observed for compound 4a at 50 μM.

Design, synthesis, and biological studies of novel 3-benzamidobenzoic acid derivatives as farnesoid X receptor partial agonist

Farnesoid X receptor (FXR), a bile acid-activated nuclear receptor, regulates the metabolism of bile acid and lipids as well as maintains the stability of internal environment. FXR was considered as a therapeutic target of liver disorders, such as drug-induced liver injury, fatty liver and cholestasis. The previous reported FXR partial agonist 6 was a suitable lead compound in terms of its high potent and low molecular size, while the docking study of compound 6 suggested a large unoccupied hydrophobic pocket, which might be provided more possibility of structure-activity relationship (SAR) study. In this study, we have performed comprehensive SAR and molecular modeling studies based on lead compound 6. All of these efforts resulted in the identification of a novel series of FXR partial agonists. In this series, compound 41 revealed the best activity and strong interaction with binding pocket of FXR. Moreover, compound 41 protected mice against acetaminophen-induced hepatotoxicity by the regulation of FXR-related gene expression and improving antioxidant capacity. In summary, these results suggest that compound 41 is a promising FXR partial agonist suitable for further investigation.

Synthetic method of Pimavanserin

The invention belongs to the field of medicine synthesis, and especially relates to a synthetic method of Pimavanserin. According to the synthetic method, 4-hydroxy benzoic acid is taken as a raw material, esterification reaction, alkylation reaction, hydrolysis, acylation reaction, dehydration reduction, and acylation reaction are carried out to obtain an intermediate (9); fluorobenzylamine and N-methyl-4-piperidone are taken as raw materials for reductive amination to obtain intermediate (10); and at last the intermediate (9) and the intermediate (10) are subjected to aminolysis to obtain finished product Pimavanserin. The initial raw materials are cheap and easily available; reaction conditions are mild; no column chromatography is needed; and the yield is relatively high.

COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES

The present disclosure relates to compounds according to Formulae disclosed herein, useful for treating diseases.

Synthesis, structure-activity relationship, and pharmacological studies of novel melanin-concentrating hormone receptor 1 antagonists 3- aminomethylquinolines: Reducing human ether-a-go-go-related gene (hERG) associated liabilities

Recently, we discovered 3-aminomethylquinoline derivative 1, a selective, highly potent, centrally acting, and orally bioavailable human MCH receptor 1 (hMCHR1) antagonist, that inhibited food intake in F344 rats with diet-induced obesity (DIO). Subsequent investigation of 1 was discontinued because 1 showed potent hERG K+ channel inhibition in a patch-clamp study. To decrease hERG K+ channel inhibition, experiments with ligand-based drug designs based on 1 and a docking study were conducted. Replacement of the terminal p-fluorophenyl group with a cyclopropylmethoxy group, methyl group introduction on the benzylic carbon at the 3-position of the quinoline core, and employment of a [2-(acetylamino)ethyl]amino group as the amine portion eliminated hERG K+ channel inhibitory activity in a patch-clamp study, leading to the discovery of N-{3-[(1R)-1-{[2-(acetylamino)ethyl]amino} ethyl]-8-methylquinolin-7-yl}-4-(cyclopropylmethoxy)benzamide (R)-10h. The compound (R)-10h showed potent inhibitory activity against hMCHR1 and dose-dependently suppressed food intake in a 2-day study on DIO-F344 rats. Furthermore, practical chiral synthesis of (R)-10h was performed to determine the molecule's absolute configuration.

COMPOSITIONS AND METHODS COMPRISING PROTEINASE ACTIVATED RECEPTOR ANTAGONISTS

Compositions and methods comprising proteinase activated receptor antagonists are provided. More particularly, the present invention relates to the use of proteins, peptides and molecules that bind to proteinase activated receptor 2, and inhibit the processes associated with the activation of that receptor. More specifically, the present invention provides novel compositions and methods for the treatment of disorders and diseases such as those associated with abnormal cellular proliferation, angiogenesis, inflammation and cancer.