60559-98-0 Usage
Uses
N-Cyano-N''-(1,1-dimethylpropyl)-N''''-3-pyridinyl-guanidine is an ATP-sensitive potassium channels activator or opener (KATPCO) by causing relaxation of various isolated animal and human blood vessels.
Biological Activity
Potent K ATP channel opener (EC 50 for relaxation of rat aorta = 7.5 nM). Binds to SUR2A and SUR2B with high affinity (K d values are 17 and 3 nM respectively).
Enzyme inhibitor
This potent potassium ion channel opener, or KCO (FW = 231.30 g/mol; CAS 60559-98-0; Solubility: 50 mM in Ethanol; 100 mM in DMSO), also known as N-cyano-N'-(1,1-dimethylpropyl)-N''-3-pyridyl-guanidine, targets Kir6 (or KATP) channels (EC50 = 7.5 nM; for relaxation of rat aorta). In studies on rats, rabbit and dogs, P1075 effects only correlate with the presence of specific receptor binding sites in rat vascular preparations, showing there are significant species-specific and raising questions about the pharmacological significance of this KATP opener binding site. These channels are heteromultimers composed with a 4:4 stoichiometry of an inwardly rectifying K+ channel subunit plus a regulatory subunit comprising the receptor sites for hypoglycemic sulfonylureas and KCOs (a sulfonylurea receptor). P1075-induced channel activation IS mediated by drug interaction with a single binding site per tetradimeric complex. P-1075 also binds to sulfonylurea receptors SUR2A (Kd = 17 nM) and SUR2B (Kd = 3 nM)
Check Digit Verification of cas no
The CAS Registry Mumber 60559-98-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,0,5,5 and 9 respectively; the second part has 2 digits, 9 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 60559-98:
(7*6)+(6*0)+(5*5)+(4*5)+(3*9)+(2*9)+(1*8)=140
140 % 10 = 0
So 60559-98-0 is a valid CAS Registry Number.
InChI:InChI=1/C12H17N5/c1-4-12(2,3)17-11(15-9-13)16-10-6-5-7-14-8-10/h5-8H,4H2,1-3H3,(H2,15,16,17)
60559-98-0Relevant articles and documents
Structure-activity studies of potassium channel opening in pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas
Manley,Quast
, p. 2327 - 2340 (2007/10/02)
Potassium channel opening activity for pinacidil-type cyanoguanidines, nitroethenediamines, thioureas, and ureas, has been assessed through simultaneous measurement of spontaneous contractile activity and stimulation of 86Rb+ efflux from rat portal veins loaded with 86Rb+. The good correlation between these two effects suggests that the vasodilator activity of the compounds is directly attributable to an increased opening of potassium channels. The resulting quantitative in vitro data has been used to analyze the structure-activity relationships for potassium channel opening, allowing the biological activity to be rationalized in terms of a pharmacophore involving a hydrogen-bond-acceptor element, a hydrogen-bond- donor element, and a lipophilic binding group. A model for the binding of pinacidil-related compounds to their potassium channel receptor has been developed, and compounds designed to test this model have been synthesized and tested. Prototropic equilibria are implicated as playing a fundamental role in determining the hydrogen-bonding ability of the compounds, and conformational changes in the receptor are invoked to explain disparities in the chiral recognition of lipophilic groups in different compounds.
