72313-37-2Relevant academic research and scientific papers
Compound as protein degradation agent and preparation method and medical application thereof
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, (2021/11/03)
The invention discloses a compound serving as a protein degrading agent and a preparation method and medical application thereof, and particularly discloses a compound represented by the formula (I) and a pharmaceutically acceptable salt thereof, and the
Discovery of 5-substituted pyrrolo[2,3- d ]pyrimidine antifolates as dual-acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: Implications of inhibiting 5-aminoimidazole-4- carboxamide ribonucleotide formyltransferase to AMPK activation and antitumor activity
Mitchell-Ryan, Shermaine,Wang, Yiqiang,Raghavan, Sudhir,Ravindra, Manasa Punaha,Hales, Eric,Orr, Steven,Cherian, Christina,Hou, Zhanjun,Matherly, Larry H.,Gangjee, Aleem
, p. 10016 - 10032 (2014/01/17)
We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese hamster ovary and KB human tumor cells. Growth inhibition was reversed completely or in part by excess folic acid, indicating that FRα is involved in cellular uptake, and resulted in S-phase accumulation and apoptosis. Antiproliferative effects of compound 8 toward KB cells were protected by excess adenosine but not thymidine, establishing de novo purine nucleotide biosynthesis as the targeted pathway. However, 5-aminoimidazole-4-carboxamide (AICA) protection was incomplete, suggesting inhibition of both AICA ribonucleotide formyltransferase (AICARFTase) and glycinamide ribonucleotide formyltransferase (GARFTase). Inhibition of GARFTase and AICARFTase by compound 8 was confirmed by cellular metabolic assays and resulted in ATP pool depletion. To our knowledge, this is the first example of an antifolate that acts as a dual inhibitor of GARFTase and AICARFTase as its principal mechanism of action.
Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transpo
Deng, Yijun,Zhou, Xilin,Desmoulin, Sita Kugel,Wu, Jianmei,Cherian, Christina,Hou, Zhanjun,Matherly, Larry H.,Gangjee, Aleem
experimental part, p. 2940 - 2951 (2010/02/28)
A series of seven 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines with bridge length variations (from 2 to 8 carbon atoms) were synthesized as selective folate receptor (FR) α and β substrates and as antitumor agents. The syntheses were accomplished
Synthesis of the Antileucemic Agents 5,10-Dideazaaminopterin and 5,10-Dideaza-5,6,7,8-tetrahydroaminopterin
Taylor, Edward C.,Harrington, Peter J.,Fletcher, Stephen R.,Beardsley, G. Peter,Moran, Richard, G.
, p. 914 - 921 (2007/10/02)
Total syntheses from pyridine precursors of 5,10-dideazaaminopterin (1) and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin (2) are described.These compounds exhibit significant in vivo activity against L1210 leukemia that comparable to that observed with meth
Interphenylene 9-thia-11-oxo-12-aza-prostanoic acids
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, (2008/06/13)
This invention relates to novel interphenylene 9-thia-11-oxo-12-azaprostanoic acid compounds, salts, and derivatives thereof. These compounds are exceptionally potent renal vasodilators and antihypertensives which are active when administered orally but which have a more specific type of biological activity than that of many of the natural prostaglandins and their synthetic analogs or derivatives.
