Synonym
SLV320; SLV-320; SLV 320; Derenofylline
IUPAC/Chemical Name
(1r,4r)-4-((2-phenyl-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexan-1-ol
InChi Key
RBZNJGHIKXAKQE-HDJSIYSDSA-N
InChi Code
InChI=1S/C18H20N4O/c23-14-8-6-13(7-9-14)20-18-15-10-11-19-17(15)21-16(22-18)12-4-2-1-3-5-12/h1-5,10-11,13-14,23H,6-9H2,(H2,19,20,21,22)/t13-,14-
SMILES Code
O[C@H]1CC[C@H](NC2=C3C(NC(C4=CC=CC=C4)=N2)=NC=C3)CC1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Derenofylline (SLV 320) is an adenosine A1 receptor antagonist, with Ki values of 1 nM, 200 nM and 398 nM for human A1, A3 and A2A receptors respectively. In addition, the receptor-binding affinities as well as enzyme inhibitory properties of SLV320 were evaluated in a series of 94 receptors and 6 phosphodiesterases (PDE1–PDE6).
In vitro activity:
In receptor binding experiments using cloned human receptors, SLV320 (for chemical structure see Figure 1) behaved as a potent and selective A1 receptor ligand with selectivity factors of 200–4000 versus other adenosine receptor subtypes (see Table 1a). The selectivity factors are higher than those of the reference A1 antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; see Table 1b). A significant binding was measured only for the high-affinity rolipram-binding site on PDE4 (from mouse brain). SLV320 caused rolipram displacement from its binding site with a Ki of 79 nm, which was 79-fold less potent compared to its binding at the A1 receptor site.
Reference: Br J Pharmacol. 2007 Aug;151(7):1025-32. https://pubmed.ncbi.nlm.nih.gov/17558436/
In vivo activity:
Therefore, the novel selective adenosine A(1) receptor antagonist SLV320 was investigated, focusing on its potential in preventing cardiomyopathy in rats with 5/6 nephrectomy. Male Sprague-Dawley rats were allocated to 4 groups of 12 rats each: 5/6 nephrectomy (5/6 NX), 5/6 NX plus SLV320 (10 mg kg(-1) d(-1) mixed with food), sham and sham plus SLV320. In rats with 5/6 NX SLV320 significantly decreased albuminuria by about 50%, but did not alter glomerular filtration rate (GFR). SLV320 normalized cardiac collagen I+III contents in 5/6 NX rats. SLV320 prevented nephrectomy-dependent rise in plasma levels of creatinine kinase (CK), ALT and AST. Blood pressure did not differ between study groups. SLV320 suppresses cardiac fibrosis and attenuates albuminuria without affecting blood pressure in rats with 5/6 nephrectomy, indicating that selective A(1) receptor antagonists may be beneficial in uraemic cardiomyopathy.
Reference: Br J Pharmacol. 2007 Aug;151(7):1025-32. https://pubmed.ncbi.nlm.nih.gov/17558436/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
250.0 |
810.69 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
308.39
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Sureechatchaiyan P, Hamacher A, Brockmann N, Stork B, Kassack MU. Adenosine enhances cisplatin sensitivity in human ovarian cancer cells. Purinergic Signal. 2018 Dec;14(4):395-408. doi: 10.1007/s11302-018-9622-7. Epub 2018 Aug 4. PMID: 30078088; PMCID: PMC6298929. 2. Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg GW, Hocher B. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol. 2007 Aug;151(7):1025-32. doi: 10.1038/sj.bjp.0707319. Epub 2007 Jun 11. PMID: 17558436; PMCID: PMC2042943.
In vitro protocol:
1. Sureechatchaiyan P, Hamacher A, Brockmann N, Stork B, Kassack MU. Adenosine enhances cisplatin sensitivity in human ovarian cancer cells. Purinergic Signal. 2018 Dec;14(4):395-408. doi: 10.1007/s11302-018-9622-7. Epub 2018 Aug 4. PMID: 30078088; PMCID: PMC6298929. 2. Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg GW, Hocher B. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol. 2007 Aug;151(7):1025-32. doi: 10.1038/sj.bjp.0707319. Epub 2007 Jun 11. PMID: 17558436; PMCID: PMC2042943.
In vivo protocol:
1. Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg GW, Hocher B. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol. 2007 Aug;151(7):1025-32. doi: 10.1038/sj.bjp.0707319. Epub 2007 Jun 11. PMID: 17558436; PMCID: PMC2042943.
1: Pang PS, Mehra M, Maggioni AP, Filippatos G, Middlebrooks J, Turlapaty P, Kazei D, Gheorghiade M; RENO-DEFEND Investigators. Rationale, design, and results from RENO-DEFEND 1: a randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure. Am Heart J. 2011 Jun;161(6):1012-23.e3. doi: 10.1016/j.ahj.2011.03.004. PubMed PMID: 21641345.
2: Mitrovic V, Seferovic P, Dodic S, Krotin M, Neskovic A, Dickstein K, de Voogd H, Böcker C, Ziegler D, Godes M, Nakov R, Essers H, Verboom C, Hocher B. Cardio-renal effects of the A1 adenosine receptor antagonist SLV320 in patients with heart failure. Circ Heart Fail. 2009 Nov;2(6):523-31. doi: 10.1161/CIRCHEARTFAILURE.108.798389. Epub 2009 Sep 24. PubMed PMID: 19919976.
3: Givertz MM. Adenosine A1 receptor antagonists at a fork in the road. Circ Heart Fail. 2009 Nov;2(6):519-22. doi: 10.1161/CIRCHEARTFAILURE.109.916072. PubMed PMID: 19919975.
4: Kiesman WF, Elzein E, Zablocki J. A1 adenosine receptor antagonists, agonists, and allosteric enhancers. Handb Exp Pharmacol. 2009;(193):25-58. doi: 10.1007/978-3-540-89615-9_2. Review. PubMed PMID: 19639278.
5: Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg GW, Hocher B. The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol. 2007 Aug;151(7):1025-32. Epub 2007 Jun 11. PubMed PMID: 17558436; PubMed Central PMCID: PMC2042943.
