37739-05-2

Usage

Uses

Used in Central Nervous System (CNS) Disorders:
CCPA is used as an adenosine A1 receptor agonist for treating central nervous system (CNS) disorders. It helps in modulating the adenosine receptors, which are involved in various physiological processes in the CNS.
Used in Cardiovascular Applications:
CCPA is used as a selective adenosine receptor agonist for inhibiting angiotensin II induced cardiomyocyte hypertrophy via the calcineurin signaling pathway. This application is particularly relevant in the context of cardiovascular health and disease management.
Used in Research and Drug Development:
CCPA is often used in combination with other adenosine receptor agonists and antagonists to resolve the functions of A1, A2A, and A3 receptor subtypes. This helps researchers and pharmaceutical companies in understanding the specific roles of these receptors and developing targeted therapies for various conditions.
Chemical Properties:
CCPA is a solid chemical compound, which contributes to its stability and ease of handling in research and pharmaceutical applications.

Biological Activity

Potent and selective adenosine A 1 receptor agonist (K i values are 0.8, 2300 and 42 nM for human A 1 , A 2A and A 3 receptors respectively; EC 50 = 18800 nM for hA 2B ). Centrally active following systemic administration in vivo .

Biochem/physiol Actions

A1 adenosine receptor agonist with high selectivity: reportedly 10,000-fold for A1 over A2 receptors.

references

[1]. lohse mj, klotz kn, schwabe u, et al. 2-chloro-n6-cyclopentyladenosine: a highly selective agonist at a1 adenosine receptors. naunyn schmiedebergs arch pharmacol, 1988, 337(6): 687-689.[2]. monopoli a, conti a, dionisotti s, et al. pharmacology of the highly selective a1 adenosine receptor agonist 2-chloro-n6-cyclopentyladenosine. arzneimittelforschung, 1994, 44(12): 1305-1312.[3]. concas a, santoro g, mascia mp, et al. anticonvulsant doses of 2-chloro-n6-cyclopentyladenosine, an adenosine a1 receptor agonist, reduce gabaergic transmission in different areas of the mouse brain. j pharmacol exp ther, 1993, 267(2): 844-851.[4]. sandoli d, chiu pj, chintala m, et al. in vivo and ex vivo effects of adenosine a1 and a2 receptor agonists on platelet aggregation in the rabbit. eur j pharmacol, 1994, 259(1): 43-49.

InChI:InChI=1/C15H20ClN5O4/c16-15-19-12(18-7-3-1-2-4-7)9-13(20-15)21(6-17-9)14-11(24)10(23)8(5-22)25-14/h6-8,10-11,14,22-24H,1-5H2,(H,18,19,20)/t8-,10-,11-,14-/m1/s1

Upstream product

• 3056-18-6 (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate 
• 1003-03-8 Cyclopentamine 
• 13276-52-3 2,6-dichloropurine riboside 
• 6979-94-8 2',3',5'-tri-O-acetyl-guanosine 
• 1277180-82-1 2',3',5'-tri-O-acetyl-O₆-(benzotriazol-1-yl)-2-chloroinosine 
• 1277176-16-5 2',3',5'-tri-O-acetyl-O₆-(benzotriazol-1-yl)guanosine 
• 920974-74-9 Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(2-chloro-6-cyclopentylamino-purin-9-yl)-tetrahydro-furan-3-yl ester 

Downstream Products

• 41552-82-3 N-cyclopentyladenosine 

Relevant academic research and scientific papers

Synthesis and utility of 2-halo-O6-(benzotriazol-1-yl)- functionalized purine nucleosides

An efficient synthesis of 2-halo-O6-(benzotriazol-1-yl)- substituted purine nucleosides has been accomplished via (benzotriazol-1-yloxy) tris(dimethylamino)phosphonium hexafluorophosphate (BOP)-mediated coupling and subsequent halogenation via diazotization of the 2-amino group of various protected guanosines and directly from guanosine itself. These products are amenable to substitution and coupling reactions in the 2- and 6-positions and, accordingly, provide efficient access to highly functionalized purine nucleosides.

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.

PARENTERALLY ADMINISTERED IMMUNE ENHANCING DRUGS

Methods of identifying compounds that modulate the conversion of AMP to adenosine by 5'-nucleotidase, ecto, and that possess particular pharmacokinetic characteristics are described herein. Methods of such compounds, and compositions comprising same, for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, are also provided.

INHIBITORS OF ADENOSINE 5'-NUCLEOTIDASE

Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment

INHIBITORS OF CD73-MEDIATED IMMUNOSUPPRESSION

Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'- nucleotidase, ecto is also provided.

MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF

Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'-nucleotidase, ecto is also provided.

METHODS OF PREVENTING, REDUCING OR TREATING MACULAR DEGENERATION

The present invention is directed to selective adenosine A1 agonist compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, reduce or prevent age-related macular degeneration.

METHOD OF PROVIDING OCULAR NEUROPROTECTION

Provided herein are compounds of Formula I, compositions comprising an effective amount of a compound of Formula I, and methods for preventing, reducing or treating retinal ganglion cell damage comprising administering an effective amount of a purine deri

COMBINATION, KIT AND METHOD OF REDUCING INTRAOCULAR PRESSURE

The present invention is directed to a combination or a kit comprising a prostaglandin analog and an adenosine receptor A1 agonist and to a method of reducing intraocular pressure (IOP) in a subject using such combination or kit. The invention is particularly directed to a combination of latanoprost marketed under the brand Xalatan? and Compound A.