68548-52-7

Upstream product

• 74448-92-3 4-(4'-chlorophenoxy)benzonitrile 
• 106-47-8 4-chloro-aniline 
• 637-87-6 1-Chloro-4-iodobenzene 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 1679-18-1 4-Chlorophenylboronic acid 
• 21120-74-1 methyl 4-(4-chlorophenoxy)benzoate 
• 106-48-9 4-chloro-phenol 
• 1194-02-1 4-fluorobenzonitrile 
• 101-79-1 4-amino-4'-chlorodiphenyl ether 
• 21120-67-2 4-(4'-chlorophenoxy)-benzoic acid 

Downstream Products

• 136186-13-5 (Z)-3-[4-(4-Chloro-phenoxy)-phenyl]-2-cyano-3-hydroxy-N-(4-trifluoromethyl-phenyl)-acrylamide 
• 73980-25-3 ethyl 4-(4-chlorophenoxy)benzoylacetate 
• 1609467-63-1 benzyl 3-(5-amino-3-(4-(4-chlorophenoxy)phenyl)-4-cyano-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1609467-64-2 5-amino-3-(4-(4-chlorophenoxy)phenyl)-1-(piperidin-3-yl)-1H-pyrazole-4-carboxamide 
• 1609465-76-0 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-(1-cyanopiperidin-3-yl)-1H-pyrazole-4-carboxamide 
• 1609465-77-1 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-[(3S)-1-cyanopiperidin-3-yl]-1H-pyrazole-4-carboxamide 
• 1609465-78-2 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-[(3R)-1-cyanopiperidin-3-yl]-1H-pyrazole-4-carboxamide 
• 1609467-05-1 1-[(3R)-1-acryloyl piperidin-3-yl]-5-amino-3-[4-(4-chlorophenoxy)phenyl]-1H-pyrazole-4-carboxamide 
• 1609468-24-7 (R)-5-amino-3-(4-(4-chlorophenoxy)phenyl)-1-(piperidin-3-yl)-1H-pyrazole-4-carboxamide 
• 1609467-06-2 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-{(3R)-1-[(2E)-4-hydroxybut-2-enoyl]piperidin-3-yl}-1H-pyrazole-4-carboxamide 
• 1609467-07-3 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-{(3R)-1-[(2E)-4-fluorobut-2-enoyl]piperidin-3-yl}-1H-pyrazole-4-carboxamide 
• 1609467-08-4 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-{(3R)-1-[(2E)-4,4-difluorobut-2-enoyl]piperidin-3-yl}-1H-pyrazole-4-carboxamide 
• 1609467-09-5 5-amino-3-[4-(4-chlorophenoxy)phenyl]-1-[(3R)-1-(2-fluoroacryloyl)piperidin-3-yl]-1H-pyrazole-4-carboxamide 
• 1609467-62-0 2-((4-(4-chlorophenoxy)phenyl)(methoxy)methylene)-malononitrile 

Relevant academic research and scientific papers

Aminopyrazole Carboxamide Bruton's Tyrosine Kinase Inhibitors. Irreversible to Reversible Covalent Reactive Group Tuning

Potent covalent inhibitors of Bruton's tyrosine kinase (BTK) based on an aminopyrazole carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive groups leading to irreversible protein adducts, cyanamide-based reversible-covalent inhibitors provided the highest combined BTK potency and EGFR selectivity. The cyanamide covalent mechanism with BTK was confirmed through enzyme kinetic, NMR, MS, and X-ray crystallographic studies. The lead cyanamide-based inhibitors demonstrated excellent kinome selectivity and rat pharmacokinetic properties.

Addressing cytotoxicity of 1,4-biphenyl amide derivatives: Discovery of new potent and selective 17β-hydroxysteroid dehydrogenase type 2 inhibitors

Four different classes of new 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) inhibitors were synthesized, in order to lower the cytotoxicity exhibited by the lead compound A, via disrupting the linearity and the aromaticity of the biphenyl moiety. Compounds 3, 4, 7a and 8 displayed comparable or better inhibitory activity and selectivity, as well as a lower cytotoxic effect, compared to the reference compound A. The best compound 4 (IC50 = 160 nM, selectivity factor = 168, LD50 ≈ 25 μM) turned out as new lead compound for inhibition of 17β-HSD2.

Synthesis and antiproliferative activity of novel 4-substituted-phenoxy-benzamide derivatives

A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibited moderate efficacy in HT29 and MGC803 cell lines. Compound 10c showed promising inhibition of hedgehog (Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.

BRUTON'S TYROSINE KINASE INHIBITORS

Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

Flavones as isosteres of 4(1H)-quinolones: Discovery of ligand efficient and dual stage antimalarial lead compounds

Malaria is responsible for nearly one million deaths annually, and the increasing prevalence of multi-resistant strains of Plasmodium falciparum poses a great challenge to controlling the disease. A diverse set of flavones, isosteric to 4(1H)-quinolones, were prepared and profiled for their antiplasmodial activity against the blood stage of P. falciparum W2 strain, and the liver stage of the rodent parasite Plasmodium berghei. Ligand efficient leads were identified as dual stage antimalarials, suggesting that scaffold optimization may afford potent antiplasmodial compounds.

Studies on antihyperlipidemic agents. I. Synthesis and hypolipidemic activities of phenoxyphenyl alkanoic acid derivatives

The alkanoic acids containing phenoxyphenyl moiety at ω-position were prepared and tested for hypolipidemic property. Some of the compounds showed hypoglycemic activity besides hypolipolipidemic one. Further study on the selected compound, 3-[4-(4-chlorophenoxy)benzoyl]propionic acid (8) revealed that it increased insulin sensitivity of adipose tissue of obese and diabetic mice (KKA(y)). The structure-activity relationship was discussed briefly.