124555-18-6

Basic information

• Product Name: GR 79236
• Synonyms: GR 79236;GR 79236X;N-[(1S, TRANS)-2-HYDROXYCYCLOPENTYL]ADENOSINE;N-[(1S,2S)-2-HYDROXYCYCLOPENTYL]ADENOSINE;GR 79236X,N-[(1S, trans)-2-Hydroxycyclopentyl]adenosine
• CAS NO: 124555-18-6
• Molecular Formula: C15H21N5O5
• Molecular Weight: 351.36
• Mol File: 124555-18-6.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 728.301 °C at 760 mmHg
• Flash Point: 394.262 °C
• Appearance: white/solid
• Density: 1.897 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.846
• Storage Temp.: 2-8°C
• Solubility: H2O: 12 mg/mL
• PKA: 13.12±0.70(Predicted)
• CAS DataBase Reference: GR 79236(CAS DataBase Reference)
• NIST Chemistry Reference: GR 79236(124555-18-6)
• EPA Substance Registry System: GR 79236(124555-18-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 124555-18-6(Hazardous Substances Data)

Usage

Uses

GR 79236 is an Adenosine A1-R agonist.

Biological Activity

Adenosine A 1 receptor agonist (K i = 3.1 nM). Anticonvulsive in mice following systemic administration in vivo .

in vitro

gr79236 is a highly potent and selective a1 receptor agonist which is originally developed for the treatment of type 2 diabetes mellitus, as a cardioprotective agent and also for peripheral arterial occlusive diseases. gr79236 inhibited catecholamine-induced lipolysis in adipocytes at low concentrations [1]

in vivo

gr79236 has a pronounced effect on nefa and tg levels in both acute and chronic animal models, thus establishing the potential of this approach for the treatment of t2d [1]. gr79236 also can inhibit neurogenic vasodilation in anaesthetized rats, inhibit electrical stimulation of superior saggital sinusinduced trigeminovascular nociceptive transmission and cgrp release in anaesthetized cats and inhibit trigeminal nociception in humans [2].

IC 50

3.1 nm (ki)

references

[1] kiesman wf, elzein e, zablocki j. a1 adenosine receptor antagonists, agonists, and allosteric enhancers. handb exp pharmacol. 2009;(193):25-58.[2] arulmani u, heiligers jp, centurión d, garrelds im, villalón cm, saxena pr. lack of effect of the adenosine a1 receptor agonist, gr79236, on capsaicin-induced cgrp release in anaesthetized pigs. cephalalgia. 2005 nov;25(11):1082-90.[3] sneyd jr, langton ja, allan lg, peacock je, rowbotham dj. multicentre evaluation of the adenosine agonist gr79236x in patients with dental pain after third molar extraction. br j anaesth. 2007 may;98(5):672-6. epub 2007 apr 7.

InChI:InChI=1/C15H21N5O5/c21-4-9-11(23)12(24)15(25-9)20-6-18-10-13(16-5-17-14(10)20)19-7-2-1-3-8(7)22/h5-9,11-12,15,21-24H,1-4H2,(H,16,17,19)/t7-,8-,9+,11+,12+,15+/m0/s1

Upstream product

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Relevant articles and documents

Discovery of Novel Adenosine Receptor Agonists That Exhibit Subtype Selectivity

A series of N6-bicyclic and N6-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N6-adamantyl substitution in combination with 5′-N-ethylcarboxamido or 5′-hydroxymethyl groups. In addition, we determined that 5′-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.

N-substituted adenosines as novel neuroprotective A1 agonists with diminished hypotensive effects

The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A1 agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine-agonists. The novel compounds featured are derived structurally from two key lead structures: 2- chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1- piperidinyl)adenosine (NNC 90-1515, 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A1 functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A1 agonists such as (R)phenylisopropyladenosine (R-PIA, 5), N- cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2- hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O- methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED50 values than for reference A1 agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1- piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P1 ligands, reinforce the fact that novel selective adenosine A1 agonists have potential in the treatment of cerebral ischemia in humans.

2,N-6-disubstituted adenosines and their antihypertensive methods of use

Compounds of formula (I) STR1 wherein X represents a hydrogen or chlorine atom, or a methyl group; and R represents a cycloalkyl or cycloalkenyl ring containing 5 to 8 carbon atoms, which ring is substituted by a hydroxy group, and is optionally substitut