Disease relevance of Dicyandiamide

• Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 1. N-Cyanoguanidine bioisosteres possessing in vivo bladder selectivity [1].
• The role of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and the ADP-ribosylation inhibitor 3-aminobenzamide (3-ABA) in the cytotoxicity induced by the novel antitumoral cyanoguanidine CHS 828 was investigated in the human lymphoma cell line U-937 GTB [2].
• It was found that the carbodiimides cyanamide and dicyandiamide dramatically lowered the temperature at which thermal dehydration of the acid led to anhydride formation [3].
• About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia [4].
• CHS 828 is a pyridyl cyanoguanidine with promising antitumor activity both in vitro and in vivo, and has previously been found especially active against tumor cells obtained from patients with B cell chronic lymphocytic leukemia [5].

High impact information on Dicyandiamide

• CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo [6].
• In competition experiments using [3H]glibenclamide as radioligand, SUR1(T1285L, M1289T) showed much higher affinity toward the cyanoguanidine openers pinacidil and P1075 than SUR1 wild type [7].
• It also highlights that small structural changes can dramatically shift the efficacy of the cyanoguanidine type of selective activators of Kir6.2/SUR2 potassium channels [8].
• Condensation of appropriately substituted (arylmethyl)triphenylphosphoranes with 4, 4-ethylenedioxycyclohexanone, followed by hydrogenation (H2/Pd-C) and acidolysis, yielded the corresponding 4-(arylmethyl)cyclohexanones, which were then condensed with cyanoguanidine to form the tetrahydroquinazolines [9].
• Structure-activity relationships for the cyanoguanidine portion of the lead cardiac selective ATP-sensitive potassium channel (KATP) opener (3) are described [10].

Biological context of Dicyandiamide

• Acid hydrolysis of the cyanoguanidine 2b yields the carbamoylguanidine 2f at ambient temperatures and the guanidine 2d at elevated temperatures [11].
• 2. A-184209 inhibited membrane potential changes evoked by the prototypical cyanoguanidine ATP-sensitive K(+) channel opener (KCO) P1075 in both vascular (A10) and urinary bladder smooth muscle cells with IC(50) values of 1.44 and 2.24 micro M respectively [12].
• The current study was conducted in order to investigate the physicochemical properties, the bioavailability, and the anticonvulsant activity of cyanoguanidinophenytoin (CNG-DPH), a structural analogue of phenytoin, which was obtained by the replacement of the urea moiety by a cyanoguanidine moiety [13].
• In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828 [14].
• The new phenotypes demonstrate more than 400-fold resistance to CHS 828 and cross-resistance to six cyanoguanidine analogs, but no resistance to nine standard drugs of different mechanistic classes or to the cytotoxic guanidines m-iodobenzylguanidine and methylglyoxal-bis(guanylhydrazone) [15].

Anatomical context of Dicyandiamide

• CONCLUSIONS: A comparison with previously published data obtained in isolated middle cerebral and basilar arteries showed that potassium channel openers of the benzopyrane and cyanoguanidine type are much more potent in pial arteries than in peripheral arteries in situ or in isolated arteries of the circle of Willis and of peripheral vascular beds [16].
• The rank order of potency of a series of benzopyran and cyanoguanidine K+ channel openers (KCOs) for causing relaxation of the PGF2 alpha-precontracted porcine coronary artery was determined [17].
• In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl-biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not [18].
• Such patients should have periodic white blood cell counts because substituting the cyanoguanidine group for the thiourea group may not eliminate the hematologic effects of the H2 receptor antagonists [19].

Associations of Dicyandiamide with other chemical compounds

• However, introduction of strongly electronegative substituents into the guanidine group reduces basicity and gives potent H2-receptor antagonists, viz. the cyanoguanidine 2b (cimetidine, "Tagamet") and nitroguanidine 2e [11].
• At pH 10 aminoiminomethanesulfonic acid reacted with itself, eventually giving N-cyanoguanidine, while at pH 13-14, elimination to cyanamide predominated [20].
• We evaluated the effect of (+)-N-(6-amino-3-pyridil)-N'-[(1S,2R,4R)-bicyclo-[2.2.1]hept-2-yl] -N"- cyanoguanidine hydrochloride (AL0671), a newly synthesized cyanoguanidine-derivative potassium channel opener, on serum lipid and lipoprotein levels in obese Zucker rats, a genetically engineered model of type IV hyperlipidemia [21].
• Interaction of a novel dihydropyridine K+ channel opener, A-312110, with recombinant sulphonylurea receptors and KATP channels: comparison with the cyanoguanidine P1075 [22].
• Bioisosteres of thiourea (cyanoguanidine), and of quinazoline (quinoline-3-carbonitrile) were synthesized and are compared for their in vitro inhibitory activity [23].

Gene context of Dicyandiamide

• Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties [24].
• The carcinogenicity of cyanoguanidine, a compound used in the production of melamine, guanidine salts and guanamine derivatives, was examined in male and female Fischer 344 rats fed CRF-1 pulverized diets containing 0, 2.5 and 5% cyanoguanidine for up to 2 yr [25].

Analytical, diagnostic and therapeutic context of Dicyandiamide

• CHS 828, a pyridyl cyanoguanidine, has been shown to exert a significant antitumor effect in preclinical tests in vitro and in vivo, and CHS 828 is in phase I/II clinical trials [26].

References