454248-55-6Relevant articles and documents
Pyrizolo[1,5-a]pyrimidine derivatives of the second-generation TRK inhibitor: Design, synthesis and biological evaluation
Fan, Weizheng,Fan, Yiqing,Jiang, Hongyu,Liu, Yan,Tang, Chunlei,Zhang, Yongjie,Zhou, Ying
, (2022/03/15)
As a receptor tyrosine kinase (RTK), tropomyosin receptor kinase (Trk) is a key drug target in solid tumors. However, the use of the First-generation Trk inhibitors was greatly restricted due to mutant drug resistance. Fortunately, the emergence of the Second-generation of Trk inhibitors has brought an effective solution to this mutant resistance, such as TPX-0005 (Repotrectinib). Here, we reported a series of pyrizolo[1,5-a]pyrimidine derivatives as the second-generation Trk inhibitors, and carried out the subsequent biological activity evaluation. Among them, the best compound 14h (IC50 = 1.40, 1.80 nM, against TrkA, TrkAG595R, respectively) and 14j (IC50 = 0.86, 6.92 nM, against TrkA, TrkAG595R, respectively) has a kinase activity comparable to TPX-0005, and 14j (IC50 = 350 nM against ALK) has a higher selectivity of Trk inhibition than TPX-0005, which may be of great significance for reducing toxicity.
Synthesis method for tert-butyl 1,2,3-oxathiazolidine-3-carboxylic ester 2,2-dioxide compound
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Paragraph 0041-0047; 0146-0152, (2020/07/13)
The invention relates to a synthesis method for a tert-butyl 1,2,3-oxathiazolidine-3-carboxylic ester 2,2-dioxide compound. The tert-butyl 1,2,3-oxathiazolidine-3-carboxylic ester 2,2-dioxide compoundhas a structural formula as shown in a formula I which is described in the specification. The synthesis method comprises the step of allowing a compound as shown in a formula II which is described inthe specification with sulfonyl chloride in the presence of an organic solvent to generate the compound as shown in the formula I. The structural formula of the compound as shown in the formula I andthe structural formula of the compound as shown in the formula II are described in the specification. The synthesis method disclosed by the invention is simple to operate; compared with a conventional published two-step method, the synthesis method provided by the invention only needs one step; and the synthesis method is more convenient, reduces byproducts, is high in yield, does not need to usea catalyst and a highly-toxic substance in the reaction, and is safe and low in cost.
CONDENSED THIOPHENE DERIVATIVES AND THEIR USE AS CYCLIC GLP-1 AGONISTS
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Page/Page column 72, (2010/02/15)
The invention provides compounds of formula (I) for use as GLP-1 receptor agonists.