4705-43-5

Upstream product

• 110-89-4 piperidine 
• 37746-78-4 4-bromo-trans-crotonic acid ethyl ester 
• 23114-90-1 (E)-4-(piperidin-1-yl)butan-2-enoic ethyl ester 

Downstream Products

• 1110813-31-4 Dacomitinib 

Relevant academic research and scientific papers

QUINAZOLINE DERIVATIVE AND USE THEREOF

The present invention relates to a series of quinazoline compounds, especially compounds as represented by formula (I), isomers thereof or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and use thereof as Pan-HER tyrosine kinase inhibitors.

2-aminopyrimidine compounds as well as pharmaceutical compositions and applications thereof

The invention discloses 2-aminopyrimidine compounds as well as pharmaceutical compositions and applications thereof. The structure of the 2-aminopyrimidine compounds is shown in the formula I, definitions of R1, R2, R3, R4, R5, X, Y, Z and W in the formula are shown in the specification and the claim. The compounds can effectively inhibit growths of a plurality of tumor cells, generate inhibition effects for EGFR and IGF1R protease, and is used for preparing antitumor drugs; the compounds can overcome drug resistance which is induced by prior medicaments Gefitinib and Erlotinib and the like, has selectivity for tumor, especially wild type non-small cell lung cancers, and has good pharmacokinetics property.

SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE

Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.

A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams), a new class of serine protease inhibitors, using acyliminium methodology

A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams) is described. The key reaction involves addition of Z-ketene acetal 24 to the acyliminium ion derived from 48. This reaction is mediated by BF3. OEt2 and introduces the 6S and 6aS stereocenters stereoselectively. The acyliminium precursor was prepared in four different ways: from racemic 2,4- diaminobutyric acid 8, from (R)-asparagine, from (R)-methionine, and via a crystallization-induced dynamic resolution of a salt of the racemic amine 56. (R)-Methionine is the preferred starting material for the preparation of enantiomerically pure material. The best conditions for addition of the ketene acetal to the acyliminium ion derived from 48 were determined by systematically screening a range of ketene acetals and Lewis acids. The best ketene acetal was Z-(1-ethoxy-3-methylbut-1-enyloxyl)triisopropylsilane 24. In this series, the bulk of the silyl group of the Z-ketene acetal can be correlated with increased 6S isopropyl product. Use of the E-ketene acetal does not lead to a significant change in stereoselectivity for the 6R isopropyl product. In contrast, variation of the Lewis acid has a considerable effect on the product stereochemistry. While BF3·OEt2 gives predominantly 6S,6aS product, AlCl3 and TiCl4 give predominantly mixtures of the 6R,6aS and 6S,6aS products and TMSOTf gives 6aR material with predominantly one unknown isopropy] isomer (trans-lactam numberings used). The synthesis can conveniently be carried out on a large scale to produce multigram quantities of the trans-lactam 28, which is a key precursor of pharmacologically active molecules such as 1, a selective and orally active human neutrophil elastase inhibitor. The overall chemical yield of 1 is 1.3%, corresponding to an average of >70% yield for each of the 14 steps, and the synthesis contains only one chromatographic purification.