F.t.i.r. spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor antagonist S-145 and related compounds. Part I

Abstract

F.t.i.r. spectra of the thromboxane A₂ receptor (TXA₂R) antagonists, S-145 (1) and BM-13177 (4) and TXA₂R agonist, U-46619 (6), have been measured in dilute CCl₄ and CHCl₃ solutions. These spectra were subjected to curve analysis to separate overlapping absorption bands. For compounds (1) and (6), the intramolecular hydrogen bonds involving twelve- and fifteen-membered rings were found between the functional groups of α- and ω-side chains, respectively. The formation ratio (p) of the intramolecular hydrogen bond in CCl₄ showed the high values of 89% for (1) and 81% for (6). For (4), the intramolecular hydrogen bond was found between the NH bond in the 2-sulphonamido group and π-electrons on the 1-phenyl group. In order to estimate ρ values of (1) and (6), the concentration dependence of the F.t.i.r. spectra of lauric acid (7) as the model compound of the α-side chain was also measured in CCl₄ and CHCl₃ solutions. The true molar absorption coefficients of OH and CO stretching bands and an association constant for (7) were determined. On the basis of information on intramolecular hydrogen bonding, the conformations of (1), (4), and (6) were examined and found to resemble each other.