828935-23-5

Upstream product

• 74-89-5 methylamine 
• 3718-88-5 3-iodobenzylamine hydrochloride 
• 793695-60-0 ethyl (1'S,2'R,3'S,4'R,5'S)-4'-(2,6-dichloropurin-9-yl)-2',3'-O-(isopropylidene)bicyclo[3.1.0]hexane-1'-carboxylate 
• 25581-41-3 D-erythronolactone acetonide 
• 189996-60-9 2,3-O-isopropylidene-D-erythrose 
• 127758-25-2 (4R,5S)-(2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)methan-1-ol 
• 127666-07-3 4,5-Dideoxy-2,3-O-isopropylidene-L-erythro-pent-4-enoic acid 
• 116669-78-4 (4S,5S)-2,2-dimethyl-5-vinyl-[1,3]dioxolane-4-carbaldehyde 
• 495397-63-2 ethyl (4S,5S)-3-[2,2-dimethyl-5-vinyl(1,3-dioxolan-4-yl)]-3-oxopropanoate 
• 828935-09-7 ethyl (1S,2R,3R,4S,5S)-3,4-O-isopropylidene-2-hydroxybicyclo[3.1.0]hexane-1-carboxylate 
• 793695-59-7 ethyl (1S,2R,3S,4S,5S)-2,3-O-isopropylidene-4-hydroxybicyclo[3.1.0]hexane-1-carboxylate 
• 696-40-2 3-iodobenzylamine 

Downstream Products

• 1037454-80-0 (1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(methoxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide 
• 1037454-82-2 (1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(hydroxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide 

Relevant academic research and scientific papers

PURINE DERIVATIVES AS A3 AND A1 ADENOSINE RECEPTOR AGONISTS

Disclosed are (N)-methanocarba adenine nucleosides of the formula: [Formula] as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1 and A3 adenosine receptors for use in cardioprotection.

A new synthetic route to (North)-methanocarba nucleosides designed as A3 adenosine receptor agonists

(Chemical Equation Presented) Activation of the A3 adenosine receptor (AR) is associated with cerebroprotective, cardioprotective, and anticancer effects. Among potent and selective A3 AR agonists are novel methanocarba adenosine analogues in which the conformation of a pseudo-ribose moiety is locked in the North (N) hemisphere of the pseudorotational cycle. 5′-Uronamide (N)-methanocarba nucleosides, such as MRS1898 and MRS2346, are examples of full agonists of the human A3 AR. An improved convergent approach from easily accessible 2,3-O-isopropylidene- D-erythrose (2b), and the combination of a strategic intramolecular cyclopropanation step plus the acid-catalyzed isomerization of an isopropylidene group, provided a suitable pseudosugar precursor (23) for the synthesis of MRS1898, MRS2346, and related analogues. This new synthetic route uses readily available building blocks and opens the way for the preparation of a variety of targets on a reasonable scale.

Ring-constrained (N)-methanocarba nucleosides as adenosine receptor agonists: Independent 5′-uronamide and 2′-deoxy modifications

Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5′-uronamide modification preserved [N6-(3-iodobenzyl)] or enhanced (N6-methyl) affinity at A3ARs, while the 2′-deoxy modification reduced affinity and efficacy in a functional assay.