163042-96-4

Usage

Uses

2-Cl-IB-MECA acts as an A3 adenosine receptor-selective nucleoside.

Biological Activity

High affinity and extremely selective A 3 adenosine receptor agonist (K i = 0.33 nM). Displays 2500- and 1400-fold selectivity over A 1 and A 2A receptors respectively. Exhibits high selectivity over the Na + -independent adenosine transporter.

InChI:InChI=1/C18H18ClIN6O4/c1-21-16(29)13-11(27)12(28)17(30-13)26-7-23-10-14(24-18(19)25-15(10)26)22-6-8-3-2-4-9(20)5-8/h2-5,7,11-13,17,27-28H,6H2,1H3,(H,21,29)(H,22,24,25)/t11-,12+,13-,17+/m0/s1

Upstream product

• 163042-90-8 2-chloro-N⁶-(3-iodobenzyl)-9-<5-(methylcarbamoyl)-2,3-di-O-benzoyl-β-D-ribofuranosyl>adenine 
• 3718-88-5 3-iodobenzylamine hydrochloride 
• 5451-40-1 2,6 dichloropurine 
• 120046-86-8 2-chloro-N-⁶-(3-iodobenzyl)adenine 
• 163042-95-3 (2-Chloro-9-trimethylsilanyl-9H-purin-6-yl)-(3-iodo-benzyl)-amine 
• 152918-18-8 N⁶-(3-iodobenzyl)adenosine-5'-N-methyluronamide 
• 1000980-71-1 ((3aR,4R,6R,6aR)-6-(2-chloro-6-(3-iodobenzylamino)9H-purine-9-yl) 2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 
• 74-89-5 methylamine 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 
• 163152-31-6 MRS 542 
• 15373-23-6 (2R,3R,4R,5R)-2-((benzoyloxy)methyl)-5-(2,6-dichloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl dibenzoate 
• 163152-42-9 2-chloro-N⁶-(3-iodobenzyl)-9-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)adenine 

Relevant academic research and scientific papers

Design and in vivo activity of A3 adenosine receptor agonist prodrugs

Prodrugs (MRS7422, MRS7476) of highly selective A3 adenosine receptor (AR) agonists Cl-IB-MECA and MRS5698, respectively, were synthesized by succinylation of the 2′ and 3′ hydroxyl groups, and the parent, active drug was shown to be readily liberated upon incubation with liver esterases. The prodrug MRS7476 had greatly increased aqueous solubility compared with parent MRS5698 and was fully efficacious and with a longer duration than MRS7422 in reversing mouse neuropathic pain (chronic constriction injury model, 3?μmol/kg, p.o.), a known A3AR effect. MRS7476 (5?mg/kg, p.o., twice daily) was found to protect against non-alcoholic steatohepatitis (NASH) in the STAM mouse model, indicated by the NAFLD activity score. Hepatocyte ballooning, IL-10 production, and liver histology were significantly normalized in the MRS7476-treated mice, but not liver fibrosis (no change in ACTA2 levels) or inflammation.?Hepatic expression of ADORA3 in human NAFLD patients was 1.9-fold lower compared to normal controls. Adora3 expression determined by qPCR in primary mouse liver was associated with the stellate cells, and its mouse full body A3AR knockout worsened liver markers of inflammation and steatosis. Thus, we have introduced a reversible prodrug strategy that enables water solubility and in vivo activity of masked A3AR agonists in models of two disease conditions.

Novel Adenine Derivatives and the Use Thereof

The present invention relates to a novel adenine derivative and a pharmaceutical use thereof and, more specifically, to a novel adenine derivative having a structure of chemical formula 1 or a pharmaceutically acceptable salt thereof, and to a composition containing the same for preventing or treating degenerative brain disease. The novel adenine derivative and the pharmaceutically acceptable salt thereof according to the present invention are adenosine A3 receptor agonists, and have an action of inhibiting the migration (or infiltration) of inflammatory cells (microglia, macrophages, neutrophils, etc.), to disease areas and the activities thereof. In addition, the adenine derivative according to the present invention was verified to suppress and treat brain injury more remarkably when compared with the known adenosine A3 receptor agonists in a cerebral ischemia experimental model, exhibit a significant effect by drug administration 10 hours after cerebral infarction, and allow long-term survival in spite of brain injury due to cerebral ischemia, and thus can be useful as an agent for treating and preventing degenerative brain disease including stroke.(AA,BB,CC,DD) Chemical formula 5COPYRIGHT KIPO 2015

Purine nucleosides

Disclosed are purine nucleoside compounds that are selective to A3 adenosine receptors and are useful for the treatment of cancer and inflammatory diseases. The compounds are shown by the following general formula (I), including isomers thereof: wherein X is sulfur or oxygen; R1 is hydrogen, alkyl, benzyl, halobenzyl, or phenylalkyl; R2 is hydrogen, halogen, alkoxy, alkenyl, alkynyl, alkylthio, or thio; R3 and R3′ are hydrogen, hydroxyalkyl, alkoxycarbonyl, or alkylaminocabonyl, whereas R3 and R3′ do not have identical substituents simultaneously; and R4 is hydrogen or alkyl. Also disclosed are a pharmaceutical composition comprising a compound of formula (I), an isomer, or its pharmacologically acceptable salt as an active ingredient and a method for preventing or treating various diseases, state, or condition, including asthma, inflammation, cerebral ischemia, heart diseases, and cancer.

2-Substitution of N6-benzyladenosine-5'-uronamides enhances selectivity for A3 adenosine receptors

Adenosine derivatives bearing an N6-(3-iodobenzyl) group, reported to enhance the affinity of adenosine-5'-uronamide analogues as agonists at A3 adenosine receptors (J. Med. Chem. 1994, 37, 636-646), were synthesized starting from methyl β-D-ribofuranoside in 10 steps. Binding affinities at A1 and A(2a) receptors in rat brain membranes and at cloned rat A3 receptors from stably transfected CHO cells were compared. N6-(3- Iodobenzyl)adenosine was 2-fold selective for A3 vs A1 or A(2a) receptors; thus it is the first monosubstituted adenosine analogue having any A3 selectivity. The effects of 2-substitution in combination with modifications at the N6- and 5'-positions were explored. 2-Chloro-N6-(3- iodobenzyl)adenosine had a K(i) value of 1.4 nM and moderate selectivity for A3 receptors. 2-Chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide, which displayed a K(i) value of 0.33 nM, was selective for A3 vs A1 and A(2a) receptors by 2500- and 1400-fold, respectively. It was 46,000-fold selective for A3 receptors vs the Na+-independent adenosine transporter, as indicated in displacement of [3H]N6-(4-nitrobenzyl)-thioinosine binding in rat brain membranes. In a functional assay in CHO cells, it inhibited adenylate cyclase via rat A3 receptors with an IC50 of 67 nM. 2- (Methylthio)-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide and 2- (methylamino)-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide were less potent, but nearly as selective for A3 receptors. Thus, 2-substitution (both small and sterically bulky) is well-tolerated at A3 receptors, and its A3 affinity-enhancing effects are additive with effects of uronamides at the 5'- position and a 3-iodobenzyl group at the N6-position.