40929-53-1

Upstream product

• 123530-61-0 ethyl 3-(5-pyrimidinyl)acrylate 
• 154844-41-4 (2E)-1,1-dimethylethyl 3-(5-pyrimidinyl)-2-propenoate 
• 1187833-38-0 (E)-butyl 3-(pyrimidin-5-yl)acrylate 
• 149520-03-6 3-pyrimidin-5-yl-acrylic acid tert-butyl ester 
• 1255703-03-7 3-pyrimidin-5-acrylate 
• 866621-24-1 (E)-methyl 3-(5-pyrimidinyl)acrylate 

Downstream Products

• 1255702-68-1 N-(4-methyl-3-(trifluoromethyl)phenyl)-4-methyl-3-(3-(pyrimidin-5-yl)acrylamido)benzamide 
• 1255703-05-9 N-(2-methyl-5-nitrophenyl)-3-(pyrimidin-5-yl)acrylamide 
• 1255703-06-0 N-(5-amino-2-methylphenyl)-3-(pyrimidin-5-yl)acrylamide 
• 1296136-94-1 (E)-N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyrimidin-5-yl)acrylamide 
• 309296-08-0 β-(5-Pyrimidinyl)-L-alanine 
• 123530-72-3 (E)-N-<4-(4-diphenylmethyl-1-piperazinyl)butyl>-3-(5-pyrimidinyl)acrylamide 
• 123530-80-3 (E)-N-<4-(4-diphenylmethylene-1-piperidinyl)butyl>-3-(5-pyrimidinyl)acrylamide 

Relevant academic research and scientific papers

Acrylamide Derivative And Use Thereof In Manufacture Of Medicament

An acrylamide derivative represented by formula (I), pharmaceutically acceptable salts and solvates thereof, as well as a medicament containing said acrylamide derivative or its pharmaceutically acceptable salts as the active ingredient, which can be used to treat disorders associated with tyrosine kinase especially Bcr-Abl, including proliferative disorders such as cancers, and inflammation and the like are provided.

Design, synthesis and biological evaluation of novel acrylamide analogues as inhibitors of BCR-ABL kinase

A series of acrylamide analogues were designed and synthesized from Imatinib and Nilotinib as novel BCR-ABL inhibitors by application of the principle of nonclassical electronic isostere. All new compounds were evaluated for their inhibitory effects on the activity of BCR-ABL kinase and the proliferation of K562 leukemia cancer cells in vitro. The acrylamide analogues in which the substituent in C ring was trifluoromethyl group were identified as highly potent BCR-ABL kinase inhibitors. Compound 13f exhibited an IC 50 value as low as 20.6 nM in ABL kinase inhibition and an IC 50 value of 32.3 nM for antiproliferative activity, about 10.5-fold and 12-fold lower than those of Imatinib respectively. These results suggest that compound 13f is a promising candidate as a novel BCR-ABL kinase inhibitor for further development.

Design, synthesis and X-ray crystallographic study of NAmPRTase inhibitors as anti-cancer agents

NAmPRTase (PBEF/Visfatin) plays a pivotal role in the salvage pathway of NAD+ biosynthesis. NAmPRTase has been an attractive target for anti-cancer agents that induce apoptosis of tumor cells via a declining plasma NAD+ level. In this report, a series of structural analogs of FK866 (1), a known NAmPRTase inhibitor, was synthesized and tested for inhibitory activities against the proliferation of cancer cells and human NAmPRTase. Among them, compound 7 showed similar anti-cancer and enzyme inhibitory activities to compound 1. Further investigation of compound 7 with X-ray analysis revealed a co-crystal structure in complex with human NAmPRTase, suggesting that Asp219 in the active site of the enzyme could contribute to an additional interaction with the pyrrole nitrogen of compound 7.

HETEROARYL DERIVATIVES AS PROTEIN KINASE INHIBITORS

Objects of the present invention are the compounds of formula I their pharmaceutically acceptable salts, enantiomeric forms, diastereoisomers and racemates, the preparation of the above-mentioned compounds, medicaments containing them and their manufacture, as well as the use of the above-mentioned compounds in the control or prevention of illnesses such as cancer.

Phenylalanine ammonia-lyase: The use of its broad substrate specificity for mechanistic investigations and biocatalysis - Synthesis of L-arylalanines

Several fluoro-and chlorophenylalanines were found to be good substrates of phenylalanine ammonialyase (PAL/EC 4.3.1.5) from parsley. The enantiomerically pure L-amino acids were obtained in good yields by reaction of the corresponding cinnamic acids with 5M ammonia solution (buffered to pH 10) in the presence of PAL. The kinetic constants for nine different fluoro-and chlorophenylalanines do not provide a rigorous proof for but are consistent with the previously proposed mechanism comprising an electrophilic attack of the methylidene-imidazolone cofactor of PAL at the aromatic nucleus as a first chemical step. In the resulting Friedel-Crafts-type σ complex the β-protons are activated for abstraction and consequently the pro-S is abstracted by an enzymic base. Results from semi-empirical calculations combined with a proposed partial active site model showed a correlation between the experimental kinetic constants and the change in polarization of the pro-S Cβ-H bond and heat of formation of the σ complexes, thus making the electrophilic attack at the neutral aromatic ring plausible. Furthermore, while 5-pyrimidinylalanine was found to be a moderately good substrate of PAL, 2-pyrimidinylalanine was an inhibitor.