69359-47-3

Usage

InChI:InChI=1/C12H17N5O4/c1-2-6-16-7-10(13)14-4-15-11(7)17(6)12-9(20)8(19)5(3-18)21-12/h4-5,8-9,12,18-20H,2-3H2,1H3,(H2,13,14,15)/t5-,8-,9-,12-/m1/s1

Upstream product

• 101904-36-3 8-ethyl-2',3'-O-isopropylideneadenosine 
• 97-93-8 triethylaluminum 
• 2946-39-6 8-bromoadenosine 
• 597-64-8 tetraethyltin 
• 60091-08-9 8-bromo-2',3',5'-(triOTMS)adenosine 
• 69359-30-4 5'-O-acetyl-8-ethoxycarbonylmethyl-2',3'-O-isopropylideneadenosine 
• 69359-29-1 5'-O-acetyl-2',3'-O-isopropylidene-8-methylsulfonyladenosine 
• 872025-37-1 2',3',5'-tris-(O-acetyl)-8-ethyladenosine 
• 101904-35-2 5'-O-acetyl-2',3'-O-isopropylidene-8-(α-ethoxycarbonylethyl)adenosine 

Relevant academic research and scientific papers

Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT)

Modification of the structure of trypanosomal AdoMetDC inhibitor 1 (MDL73811) resulted in the identification of a new inhibitor 7a, which features a methyl substituent at the 8-position. Compound 7a exhibits improved potencies against both the trypanosomal AdoMetDC enzyme and parasites, and better blood brain barrier penetration than 1.

New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine

S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical enzyme in the polyamine biosynthetic pathway and depends on a pyruvoyl group for the decarboxylation process. The crystal structures of the enzyme with various inhibitors at the active site have shown that the adenine base of the ligands adopts an unusual syn conformation when bound to the enzyme. To determine whether compounds that favor the syn conformation in solution would be more potent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituents at the 8-position of adenine were synthesized and analyzed for their ability to inhibit hAdoMetDC. The biochemical analysis indicated that an 8-methyl substituent resulted in more potent inhibitors, yet most other 8-substitutions provided no benefit over the parent compound. To understand these results, we used computational modeling and X-ray crystallography to study C8-substituted adenine analogues bound in the active site.

INHIBITORS OF S-ADENOSYL-L-METHIONINE DECARBOXYLASE

Novel mechanism-based inhibitors of S-adenosyl-L-methionine decarboxylase are provided. These compounds of formula (1) inhibit the life cycle of trypanosomes, and are useful to treat subjects infected with African trypanosomes. The invention includes pharmaceutical compositions and methods of using the compounds of formula (1).

PURINE NUCLEOTIDE DERIVATIVES

This invention provides novel 8-carbyl substituted cAMPS and a novel procedures for the preparation of 8-Br-cAMP, a key starting material.

Antiviral Activity of C-Alkylated Purine Nucleosides Obtained by Cross-Coupling with Tetraalkyltin Reagents

2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides.The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure.The 6-alkylated-9-β-D-ribofuranosylpurines as well as 2-ethyladenosine were cytotoxic at relatively low concentrations (0.8-10 μg/mL). 8-Methyladenosine was a potent and selective inhibitor of vaccinia virus, whereas 8-ethyl- and 8-vinyladenosine were specifically inhibitory to respiratory syncytial virus. 8-Vinyladenosine displayed particular activity against herpes simplex virus (type 1).

Straightforward C-8 alkylation of adenosine analogues with tetraalkyltin reagents

A one step synthesis of the 8-methyl-, 8-ethyl- and 8-vinyl derivatives of adenosine, 2'-deoxyadenosine and 2',3'-dideoxyadenosine starting from the readily available 8-bromo congeners is described. This reaction makes use of a transient silylation procedure and a Pd(0) catalysed cross-coupling with tetraorganotin reagents.