Preparation of novel pyrrolodihydroisoquinolines as inhibitors of cellular proliferation and inducers of apoptosis in cancer cells.

Abstract

The title compds. I [R1 = halo, NO2, NH2, etc.; R2 = H, halo, alkoxy; R3 = H, alkoxy; or R2 and R3 together form alkylenedioxy bridge; or R1 and R2 together form alkylenedioxy bridge and R3 = H; R4, R41 = H, alkyl; R5, R51 = H; R6 = alkyl or alkyl substituted by R61; R61 = alkoxycarbonyl, carboxyl; R7 = Ph, naphthyyl, etc.; R8 = C(O)R9; R9 = alkyl, cycloalkyl, cycloalkylalkyl or phenylalkyl] which are efficacious inhibitors of cellular (hyper)proliferation and/or inducers of apoptosis in cancer cells, were prepd. Thus, reacting 1-(6,7-dimethoxy-3,4-dihydro-2H-isoquinolin-1-ylidene)butan-2-one (prepn. given) with nitroethane and 4-hydroxy-3,5-dimethylbenzaldehyde afforded 1-[2-(4-hydroxy-3,5-dimethylphenyl)-8,9-dimethoxy-3-methyl-5,6-dihydro-pyrrolo[2,1-a]isoquinolin-1-yl]propan-1-one which showed -logIC50 in the range from 5.8 to 6.8 when tested on NCI-H460 non-small cell lung cancer cells. Pharmaceutical formulations comprising the compd. I alone or in combination with other therapeutic agents are disclosed. [on SciFinder(R)]