Preparation of 2-(2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyls as sodium ion proton antiporter (NHE) inhibitors.

Abstract

Title compds. I [R1, R2, R3, R4 = H, halo, CN, etc.; R5 = H, CpH2p+1, CssH2ss-1, etc.; p = 1-8; ss = 3-8; R6 = H, halo, OH, etc.; R7, R8, R9 = Ov-SOw-R23; v = 0, 1; w = 0-2, R23 = OH, CnnH2nn+1, CmmH2mm-1, etc.; nn = 1-8] and their pharmaceutically acceptable salts were prepd. For example, acid catalyzed intramol. Pictet Spengler cyclization of benzyl alc. II, prepd. from N-methyl-2,4-dichlorobenzylamine in 3-steps, afforded claimed phenyltetrahydroisoquinoline III. In proton sodium antiporting protein (NHE3) inhibition studies, 27-examples of compds. I exhibited IC50 values ranging from 0.024-1.507 μM, e.g., the IC50 value of phenyltetrahydroisoquinoline III hydrochloride was 0.075 μM. Compds. I can also influence serum lipoproteins and can be used for the regression of atherosclerotic alterations. [on SciFinder(R)]