Preparation of benzimidazole derivatives for treatment of prostatic hypertrophy.

Abstract

5-[(Pyridin-5-ylcarbonyl)amino]-1H-benzimidazole compds. represented by the general formula [I; wherein R1 and R2 each represents H, (un)substituted C1-6 alkyl, or (un)substituted C3-7 cycloalkyl, provided that R1 and R2 may form, in cooperation with the adjacent nitrogen atom, a 4- to 8-membered (un)substituted heterocycle optionally having N or O besides that nitrogen atom in the ring structure; and R3 represents a 5- or 6-membered monocyclic unsatd. heterocyclic group having, in the ring structure, one to three heteroatoms selected among N, O, and S, benzofuryl, dihydrobenzofuryl, methylenedioxyphenyl (these groups are (un)substituted)] or pharmaceutically acceptable salts thereof are prepd. These compds. or salts thereof are useful in the prevention or treatment of diseases attributable to abnormal proliferation of prostatic interstitial cells, in particular, prostatic hypertrophy (benign prostatic hyperplasia). Thus, N-(3,4-diaminophenyl)-6-morpholinonicotinamide was cyclocondensed with 2-dimethylaminomethylpyridine-5-carboxaldehyde to give 2-[(2-dimethylaminomethyl)pyridin-5-yl]-5-[[2-(morpholino)pyridin-5-yl]carbonylamino]-1H-benzimidazole (II). II showed IC50 of 0.025 μM against the proliferation of prostatic interstitial cells. Pharmaceutical formulation contg. specific compds. I were described. [on SciFinder(R)]