US 6,444,812 B1 · Intermediate compounds in the preparation of farnnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N-or C linked imidazoles

Abstract

This invention concerns intermediates in the preparation of compounds of formula the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein the dotted line represents an optional bond; X is oxygen or sulfur; —A— is a bivalent radical of formula; R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar, Ar—C1-6alkyl, Ar-oxy, Ar—C1-6alkyloxy; or when on adjacent positions R1 and R2 taken together may form a bivalent radical; R3 and R4 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy, Ar-oxy, C1-6alkylthio, di(C1-6alkyl)amino, trihalomethyl, trihalomethoxy, or when on adjacent positions R3 and R4 taken together may form a bivalent radical; R5 is an imidazolyl substituted with hydrogen or C1-6alkyl; R6 hydrogen, hydroxy, halo, cyano, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl or Ar; or a radical of formula —O—R7, —S—R8, —N—R8R9; and Ar is optionally substituted phenyl; and of the preparation, thereof.

Claims2

Dependent claims

A compound of formula (VI)

an acid addition salt or a stereochemically isomeric form thereof, wherein
X, R1, R2 and —A— are as follows:
X is oxygen or sulfur;
—A— is a bivalent radical of formula
—CH═CH— (a-1), —CH2—S— (a-6), —CH2—CH2— (a-2), —CH2—CH2—S— (a-7), —CH2—CH2—CH2— (a-3), —CH═N— (a-8), —CH2—O— (a-4), —N═N— (a-9), or —CH2—CH2—O— (a-5), —CO—NH— (a-10);
wherein optionally one hydrogen atom may be replaced by C1-4 alkyl or Ar1;
and
R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6 alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyl-oxy, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar2, Ar2-C1-6alkyl, Ar2-oxy, Ar2-C1-6alkyloxy;
or
when on adjacent positions R1 and R2 taken together may form a bivalent radical of formula
—O—CH2—O— (b-1), —O—CH2—CH2—O— (b-2), —O—CH═CH— (b-3), —O—CH2—CH2— (b-4), —O—CH2—CH2—CH2— (b-5), or —CH═CH—CH═CH— (b-6)
with the proviso that when R1 is hydrogen R2 is not hydrogen.

9 more elements

Dependencies are inferred from the claim text.

Intermediate compounds in the preparation of farnnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N-or C linked imidazoles

Life of this patent

Intermediate compounds in the preparation of farnnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N-or C linked imidazoles

Life of this patent

Abstract

Claims2