NOVEL COMPOUND HAVING PYRROLE RING AND INHIBITING FARNESYL TRANSFERASE, PHARMACEUTICALLY ACCEPTABLE SALT, HYDRATE, SOLVATE AND ISOMER THEREOF, METHOD FOR PREPARING THE SAME

摘要

PURPOSE: A novel compound having the pyrrole ring and inhibiting farnesyl transferase, its pharmaceutically acceptable salt, hydrate, solvate and isomer are provided. And their preparation method is also provided. The farnesyl transferase inhibitors have anticancer activity, restenosis inhibiting activity, hyperlipidemia inhibiting activity and antiviral activity. CONSTITUTION: The compound as a farnesyl transferase inhibitor is represented by the formula(1), wherein n is 0, 1 or 2; X is C or N; R1 is hydrogen or methyl; R2 is lower alkyl, halogen optionally substituted phenyl, or naphthyl; and R3 is selected from the formula of N-R5-N-R5-R6, N-R5-Y-R6 or N-Y ring in which Y is O, S, S=O or SO2, R5 and R6 are independently hydrogen, hydroxyl, lower alkyl or lower alkoxy, and R4 is lower alkyl, alkoxyalkyl, cycloalkyl, cycloalkyl substituted lower alkyl or hetero aromatic ring substituted lower alkyl, or OR7 in which R7 is lower alkyl, alkoxyalkyl, morpholinyl, morpholinyl substituted lower alkyl, N-methylpiperazinyl substituted lower alkyl or alkenyl. The method for preparing the compound of the formula(1) comprises the steps of: reacting a compound of the formula(2) with (a) L-R4 in which L is halogen, (b) CHO-R4 or ketone compound in the presence of sodium triacetoxy borohydride, or (c) L-C(O)(CH2)n-L in which n is an integer of 1 to 5; and substituting the reaction product with morpholine or piperazine.