7193-87-5

Usage

Synthesis Reference(s)

Synthetic Communications, 22, p. 2927, 1992 DOI: 10.1080/00397919208021116

InChI:InChI=1/C9H14N2O2/c1-4-12-8-7(3)6-10-9(11-8)13-5-2/h6H,4-5H2,1-3H3

Upstream product

• 98546-80-6 2-ethanesulfonyl-4-chloro-5-methyl-pyrimidine 
• 141-52-6 sodium ethanolate 
• 1780-31-0 2,6-dichloro-5-methylpyrimidine 
• 64-17-5 ethanol 
• 99516-33-3 4-ethoxy-2-ethylsulfanyl-5-methyl-pyrimidine 
• 13480-95-0 2-ethylthio-3,4-dihydro-5-methylpyrimidin-4-one 
• 13480-96-1 4-chloro-2-ethylsulfanyl-5-methyl-pyrimidine 
• 65-71-4 thymin 
• 64-67-5 diethyl sulfate 
• 114536-12-8 2-ethanesulfonyl-4-ethoxy-5-methyl-pyrimidine 

Downstream Products

• 6220-45-7 4-ethoxy-1,5-dimethyl-1H-pyrimidin-2-one 
• 25307-94-2 1,5-dimethyl-4-methylamino-1H-pyrimidin-2-one 
• 3258-09-1 α-thymidine 
• 3180-78-7 1-(β-D-glucopyranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione 
• 2140-61-6 4-amino-5-methyl-1-α-D-ribofuranosyl-1H-pyrimidin-2-one 

Relevant academic research and scientific papers

Structurally Simple, Readily Available Peptidomimetic 1-Benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1 H)-one Exhibited Efficient Cardioprotection in a Myocardial Ischemia (MI) Mouse Model

TLR4, a member of the Toll-like receptor (TLR) family, serves as a pattern recognition receptor in the innate immune response to microbial pathogens. TLR4 also regulates the inflammatory reaction to ischemic injury in the heart. The TRIF-related adaptor molecule (TRAM) is an adapter that recruits the Toll/interleukin 1 receptor (TIR) domain, which contains adapter-inducing IFN-β (TRIF), to activate TLR4, following TRIF-dependent cytokine gene transcription. On the basis of a known TRAM-derived decoy peptide, 10 of its peptidomimetics were synthesized. One of them, 1-benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one (21), exhibited high potency and efficacy in vitro. In vitro results and in silico analysis provided evidence for the possible direct interaction of 21 with the TLR4 complex. Administered in mice, 21 was able to block the pathophysiological manifestation of MI, restoring the concomitant tissue damage, with a 100% survival rate. Thus, inhibition of TLR4-mediated inflammation in postischemic myocardium could be used as an approach for developing cardioprotective drugs.

TOLL-LIKE RECEPTOR 4 (TLR4) INHIBITORS AND USE THEREOF

Peptides, peptidomimetics and small molecules, collectively referred to as "decoy peptides", are provided, which interfere with binding to a TIR domain of a toll-like receptor 4 (TLR4), and inhibit a TLR4-induced signaling pathway. These decoy peptides may be useful for treating diseases associated with induction of TLR4 signaling pathway such as a disease or disorder secondary to a cardiovascular disease, sepsis or an inflammatory disease.

HSAB-driven chemoselective N1-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives

The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1H)-pyrimidinones 1-3 undergo highly chemoselective N1-methylation or ethylation when treated with methyl- or ethylsulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O2-alkylation. Potassium salts of the same bases in DMF undergo prevalent O2-attack. Under the same conditions, a similar but less chemoselective behaviour is observed in alkylation of thymine and uracil, where some N3-attack occurs. This can be rationalised in terms of the HSAB principle.

The facile synthesis of N(1),N(4)-dimethyl-5-substituted cytosines

A facile, high yield synthesis of N(1),N(4)-dimethyl-5-alkyl (methyl, ethyl, n-propyl, n-butyl) cytosines has been described. This method seems to be an alternative and universal route to N(1),N(4)-methylated cytosines with any 5-substituent.