| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
Adenosine A1 receptor (IC50 = 1.8 nM); Adenosine A2 receptor (IC50 = 114 nM)
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| ln Vitro |
Six amine, amino acid and peptide derivatives derived from 1,3-dipropyl-8-(p-carboxymethylphenyl)xanthine, a functionalized congener of 1,3-dipropyl-8-phenylxanthine, have been investigated as antagonists at A2 adenosine receptors stimulatory to adenylate cyclase in membranes from rat pheochromocytoma PC 12 cells and human platelets and at A1 adenosine receptors inhibitory to adenylate cyclase from rat fat cells. The functionalized congeners and conjugates have affinity constants ranging from 80 to 310 nM at A2 receptors of PC 12 cells and from 25 to 135 nM at those of platelets. The affinity of the xanthine derivatives at A1 receptors of fat cells are in the 15 to 30 nM range. Thus, the amino acid and peptide conjugates have high potencies at both receptor subclasses and show some selectivity toward A1 adenosine receptors. Derivatives of the congeners should be useful as receptor probes and as radioiodinated ligands [1].
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| ln Vivo |
The convulsant properties of xanthine amine congener (XAC, 8-(4-(2-aminoethyl)-aminocarboxylmethyloxy)phenyl-1,3-dipropylxant hine) are compared to those of caffeine. Male Swiss albino mice were infused with convulsants through a lateral tail vein. Convulsion thresholds (i.e. the amount of convulsants required to elicit convulsions) of 39.8 +/- 2.0 mg/kg (n = 10) and 109.8 +/- 2.3 mg/kg (n = 10) were calculated for XAC and caffeine respectively. Pretreatment of animals with the adenosine receptor agonists 2-chloroadenosine, N6-cyclohexyladenosine or 5'-N-ethylcarboxamido-adenosine (1 mg/kg, i.p., 20 minutes prior to infusion) significantly decreased the seizure threshold of both XAC and caffeine. The adenosine uptake blockers, 6-nitrobenzylthioinosine or dipyridamole (0.25 mg/kg, i.p., 20 minutes prior to infusion) did not significantly affect the seizure threshold to either XAC or caffeine. The benzodiazepine agonist diazepam (5 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to both XAC (p less than 0.05) and caffeine (p less than 0.01), whereas the benzodiazepine antagonist Ro 15-1788 (10 mg/kg, i.p., 20 minutes prior to infusion) significantly increased the seizure threshold to caffeine (p less than 0.01), but not XAC. The results suggest that actions at benzodiazepine receptors may be a tenable hypothesis to explain the convulsant actions of caffeine, but not those of XAC.[2]
In infusion studies, theophyllin or caffeine were not as effective as xanthine amine congener dihydrochloride as a convulsant at a dosage of 39.8 mg/kg. When given intraperitoneally (i.p.), XAC has no effect; the seizure threshold is greater than 1000 mg/kg[2]. |
| Enzyme Assay |
Adenylate cyclase assay [1]
Adenylate cyclase activity was assayed in a medium containing 0.1 mM [α-32P]ATP (0.3–0.4 μCl/tube), 0.1 mM cyclic AMP, 1 μg/ml adenosine deaminase, 0.1 mM rolipram (4-(3-cyclopentyloxy-4-metnoxyphenyl)-2-pyrrolidinone; ZK 62,711), 0.2 mM EGTA, 5 mM creatine phosphate as Tris-salt, 0.4 mg/ml creatine kinase, 2 mg/ml bovine serum albumin and 50 mM Tris-HCl, pH 7.4, in a total volume of 100 μl. The concentrations of GTP and MgCl2 were 10 μM and 0.5 mM for PC 12 cell membranes, 1 μM and 1 mM for platelet membranes and 10 μM and 1 mM for fat cell membranes, respectively. In the case of fat cell membranes, 150 mM NaCl was included in the assay. Incubations were initiated by the addition of PC 12 cell membranes (approximately 5–10 μg protein/tube), human platelet membranes (approximately 10–15 μg protein/tube) or rat fat cell membranes (approximately 5 μg protein/tube) to reaction mixtures that had been preincubated for 5 min at 37°C and were conducted for 10 min at 37°C. Reactions were stopped by addition of 0.4 ml 125 mM zinc acetate and 0.5 ml 144 mM Na2CO3. Under these conditions, cyclic AMP formation was linear as a function of time for at least 10 min Cyclic AMP was purified as described previously. |
| Cell Assay |
Preparation of pheochromocytoma (PC 12) cell membranes [1]
PC 12 cells, derived from a pheochromocytoma tumor of the rat adrenal medulla, were used. The cells were grown in plastic tissue culture flasks in Dulbecco’s modified Eagle’s medium with 6% fetal calf serum, 6% horse serum and a penicillin-streptomycin mixture. The cells were kept at 37°C in an atmosphere enriched in CO2. After washing the cells twice with buffer (10 mM Tris-HCl, 150 mM NaCl, 1 mM EDTA, pH 7.4), membranes were prepared by homogenizing cells in 5 mM Tris-HCl, 1 mM EDTA, pH 7.4, using a Polytron homogenizer at a setting of 6 for 10 sec. The homogenate was centrifuged at 1,000 × g for 10 min and the supernatant again centrifuged at 39,000 × g for 20 min. The pellet was resuspended in 5 mM Tris-HCl, 1 mM EDTA, pH 7.4, and centrifuged at 39,000 × g for 20 min. Finally, the membranes were resuspended in 50 mM Tris-HCl, pH 7.4, frozen in liquid nitrogen and stored at −70°C Protein was measured according to the method of Lowry. Preparation of human platelet membranes [1] Platelet membranes were prepared as described by Tsai and Lefkowitz. Preparation of rat fat cell membranes [1] Isolated rat fat cells were prepared according to the method of Rodbell Plasma membranes were prepared as described by McKeel and Jarett. |
| Animal Protocol |
Animal/Disease Models: Mice[2]
Doses: 39.8 mg/kg Route of Administration: Infusion injection; single dose Experimental Results: Acted as a convulsant agent than either caffeine or theophyllin. |
| References |
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| Additional Infomation |
The general structure of the functionalized congeners of 1,3-dipropyl-8-phenylxanthine is shown in Fig. 2 (see Table I for structures). The potencies of these congeners and other xanthines as antagonists at A2 adenosine receptors of PC 12 membranes was determined versus the NECA-stimulated adenylate cyclase activity in membranes. The effects of the xanthine amine congener (XAC ) 8 and the D-lysine conjugate 9 on the concentration-response curve of NECA for stimulation of adenylate cyclase activity are shown in Fig. 3A NECA stimulated enzyme activity with an EC50 of 170 nM. The amine congener XAC did not affect basal activity in the absence of NECA, but produced a parallel shift of the concentration-response curve to the right without a change of slope or maximal effect. This is consistent with a competitive antagonism. The EC50 of NECA in the presence of 0.5 μM of the XAC was 1.25 μM. The KB of the antagonist calculated from the Schild equation for this experiment was 179 nM (see Table I). The D-lysine conjugate 9 was somewhat less potent and had a KB of 152 nM for this experiment.
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| Molecular Formula |
C21H29CLN6O4
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|---|---|
| Molecular Weight |
464.95
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| Exact Mass |
464.193
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| CAS # |
1783977-95-6
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| Related CAS # |
1783977-95-6 (HCl); 1962928-23-9 (2HCl); 96865-92-8 (3HCl)
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| PubChem CID |
89701119
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
32
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| Complexity |
639
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IVOSTHCDPHGPAS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H28N6O4.ClH/c1-3-11-26-19-17(20(29)27(12-4-2)21(26)30)24-18(25-19)14-5-7-15(8-6-14)31-13-16(28)23-10-9-22;/h5-8H,3-4,9-13,22H2,1-2H3,(H,23,28)(H,24,25);1H
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| Chemical Name |
N-(2-aminoethyl)-2-[4-(2,6-dioxo-1,3-dipropyl-7H-purin-8-yl)phenoxy]acetamide;hydrochloride
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| Synonyms |
1783977-95-6; N-(2-Aminoethyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy)acetamide hydrochloride; Xanthine amine congener (hydrochloride); XAC (hydrochloride); SCHEMBL15124872; Xanthine amine congener hydrochloride;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~20.83 mg/mL (~44.80 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1508 mL | 10.7538 mL | 21.5077 mL | |
| 5 mM | 0.4302 mL | 2.1508 mL | 4.3015 mL | |
| 10 mM | 0.2151 mL | 1.0754 mL | 2.1508 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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