For research use only. Not for therapeutic Use.
UK 357903 is a PDE5A inhibitor potentially for the treatment of erectile dysfunction
| Catalog Number | I009933 |
| CAS Number | 247580-98-9 |
| Synonyms | UK-357903; UK357903; UK 357903;3-ethyl-5-(5-((4-ethylpiperazin-1-yl)sulfonyl)-2-(2-methoxyethoxy)pyridin-3-yl)-2-(pyridin-2-ylmethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one |
| Molecular Formula | C27H34N8O5S |
| Purity | ≥95% |
| Target | PDE5A inhibitor |
| Solubility | Soluble in DMSO |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| InChI | InChI=1S/C27H34N8O5S/c1-4-22-23-24(32-35(22)18-19-8-6-7-9-28-19)26(36)31-25(30-23)21-16-20(17-29-27(21)40-15-14-39-3)41(37,38)34-12-10-33(5-2)11-13-34/h6-9,16-17H,4-5,10-15,18H2,1-3H3,(H,30,31,36) |
| InChIKey | QDPNAMRLQRQPMR-UHFFFAOYSA-N |
| SMILES | O=C1C2=NN(CC3=NC=CC=C3)C(CC)=C2N=C(C4=CC(S(=O)(N5CCN(CC)CC5)=O)=CN=C4OCCOC)N1 |
| Reference | 1:Br J Pharmacol. 2004 Jan;141(1):114-22. Epub 2003 Dec 8. Haemodynamic effects of the selective phosphodiesterase 5 inhibitor, UK-357,903, in conscious SHR.Gardiner SM,March JE,Kemp PA,Ballard SA,Hawkeswood E,Hughes B,Bennett T, PMID: 14662738 PMCID: PMC1574167 DOI: 10.1038/sj.bjp.0705581 </br><span>Abstract:</span> 1. Regional haemodynamic responses to a continuous, 4-day infusion of the selective phosphodiesterase type 5 inhibitor, UK-357,903 (0.133 or 1.33 mg x kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats, and compared with those of enalapril (1 mg x kg(-1) h(-1)). 2. Both doses of UK-357,903 caused modest reductions in mean blood pressure that were not dose-dependent and only significantly different from the vehicle effects on Day 1 of the study (mean -11.8 and -15.3 mmHg for low and high doses, respectively). UK-357,903 had mesenteric and hindquarters vasodilator effects, which were, again, similar for both dose levels and only significantly different from vehicle on Day 1. Neither dose of UK-357,903 affected renal vascular conductance or heart rate. 3. Although the haemodynamic effects of UK-357,903 were not clearly dose-related and some appeared to wane with time, geometric mean plasma levels of UK-357,903 increased in proportion to dose, and were sustained throughout the infusion period. Furthermore, plasma cyclic guanosine monophosphate, a biomarker of phosphodiesterase 5 inhibition, was persistently elevated, and increased with increasing dose. 4. Enalapril caused a fall in mean blood pressure on day 1 (-14.1 mmHg) that was associated with dilatation in renal, mesenteric and hindquarters vascular beds. The haemodynamic effects of enalapril were sustained or increased over the 4-day infusion, although plasma free drug levels were stable. 5. In conclusion, we have shown regional and temporal changes in the haemodynamic effects of UK-357,903, which may be due to activation of compensatory mechanisms, but there were no signs of functional compensation to the cardiovascular effects of enalapril. |
