23558-62-5

Usage

Uses

Used in Pharmaceutical Industry:
(2R,3R,4S,5R)-2-(6-(benzylamino)-2-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol is used as a potential pharmaceutical candidate for [application reason]. Its purine structure may offer biological activity, and the hydroxymethyl group could be involved in binding to target molecules or enhancing solubility. The benzylamino group may also contribute to specific interactions with biological systems, making it a promising compound for drug development.
Used in Chemical Research:
In the field of chemical research, (2R,3R,4S,5R)-2-(6-(benzylamino)-2-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol serves as a subject for studying the effects of stereochemistry on molecular properties and reactivity. Its complex structure allows for investigations into the role of functional groups and their influence on chemical behavior, which can be valuable for the development of new synthetic methods or the understanding of molecular recognition processes.

Upstream product

• 100-46-9 benzylamine 
• 13276-52-3 2,6-dichloropurine riboside 
• 3056-18-6 (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate 

Downstream Products

• 864062-03-3 C₁₈H₂₁N₅O₅ 
• 53081-10-0 (2R,3R,4S,5R)-2-(6-(benzylamino)-2-(methylthio)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 

Relevant academic research and scientific papers

Discovery of Potent and Selective Methylenephosphonic Acid CD73 Inhibitors

Solid tumors are often associated with high levels of extracellular ATP. Ectonucleotidases catalyze the sequential hydrolysis of ATP to adenosine, which potently suppresses T-cell and NK-cell functions via the adenosine receptors (A2a and A2b). The ectonucleotidase CD73 catalyzes the conversion of AMP to adenosine. Thus, increased CD73 enzymatic activity in the tumor microenvironment is a potential mechanism for tumor immune evasion and has been associated with poor prognosis in the clinic. CD73 inhibition is anticipated to restore immune function by skirting this major mechanism of adenosine generation. We have developed a series of potent and selective methylenephosphonic acid CD73 inhibitors via a structure-based design. Key binding interactions of the known inhibitor adenosine-5′-(α,β-methylene)diphosphate (AMPCP) with hCD73 provided the foundation for our early designs. The structure-activity relationship study guided by this structure-based design led to the discovery of 4a, which exhibits excellent potency against CD73, exquisite selectivity against related ectonucleotidases, and a favorable pharmacokinetic profile.

Discovery of AB680: A Potent and Selective Inhibitor of CD73

Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure-activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (Ki = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclinical species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clinical trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human.

CD73 INHIBITORS AND PHARMACEUTICAL USES THEREOF

CD73 (also known as ecto-5′-nucleotidase) inhibitor compounds are provided, as well as compositions and uses thereof for treating or preventing CD73-associated or related diseases, disorders and conditions, including cancer- and immune-related disorders. CD73 inhibitor compounds include compounds having the structure set forth in Formula I and pharmaceutically acceptable esters or salts thereof.

CD73 Inhibitor and pharmaceutical application thereof

The present invention provides a compound of a formula (I) and its pharmaceutically acceptable salt and ester thereof, as well as a pharmaceutical composition thereof, the use of said compound and thepharmaceutical composition thereof for the treatment and/or prevention of CD73-related diseases, disorders and conditions, including cancer-related and immune-related disorders.