Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure-Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α2-Adrenoceptor was written by Grunewald, Gary L.;Dahanukar, Vilas H.;Jalluri, Ravi K.;Criscione, Kevin R.. And the article was included in Journal of Medicinal Chemistry in 1999.HPLC of Formula: 82771-59-3 The following contents are mentioned in the article:
7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the α2-adrenoceptor. To design a selective (PNMT vs α2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and α2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quant. structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599π – 0.0725MR + 1.55σm + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the α2-adrenoceptor (α2 pKi = 0.599π – 0.0542MR – 0.951σm + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative mol. field anal. (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the α2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs α2-adrenoceptor affinity) inhibitors of PNMT. This study involved multiple reactions and reactants, such as 1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3HPLC of Formula: 82771-59-3).
1-(1,2,3,4-Tetrahydroisoquinolin-7-yl)ethanone (cas: 82771-59-3) belongs to tetrahydroisoquinoline derivatives. The tetrahydroisoquinoline skeleton is present in a number of drugs, such as tubocurarine, one of the quaternary ammonium muscle relaxants. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.HPLC of Formula: 82771-59-3
Referemce:
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem