Identification of a Potent Sodium Hydrogen Exchanger Isoform 1 (NHE1) Inhibitor with a Suitable Profile for Chronic Dosing and Demonstrated Cardioprotective Effects in a Preclinical Model of Myocardial Infarction in the Rat was written by Huber, John D.;Bentzien, Jorg;Boyer, Stephen J.;Burke, Jennifer;De Lombaert, Stephane;Eickmeier, Christian;Guo, Xin;Haist, James V.;Hickey, Eugene R.;Kaplita, Paul;Karmazyn, Morris;Kemper, Raymond;Kennedy, Charles A.;Kirrane, Thomas;Madwed, Jeffrey B.;Mainolfi, Elizabeth;Nagaraja, Nelamangara;Soleymanzadeh, Fariba;Swinamer, Alan;Eldrup, Anne B.. And the article was included in Journal of Medicinal Chemistry in 2012.Formula: C9H6BrF3O2 This article mentions the following:
Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethylbenzoyl]guanidine (I). Pharmacol. evaluation of I revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8Formula: C9H6BrF3O2).
Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon–bromine bond is electrophilic in nature. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Formula: C9H6BrF3O2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary