학술논문
Keto amide derivatives useful as farnesyl protein transferase inhibitors
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Patent
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Abstract
Compounds of the following formula useful for inhibiting Ras function and therefore inhibiting or treating the abnormal growth of cells are disclosed: ##STR1## or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, wherein
R and R.sup.2 are halo;
R.sup.1 and R.sup.3 are H and halo, provided that at least one of R.sup.1 and R.sup.3 is H;
X is N, CH or C, when the double bond is present at the C-11 position;
R.sup.4 is=O, --NHOH, --N.dbd.NHR.sup.6, --N.dbd.NHSO.sub.2 R.sup.6, --N.dbd.NHCOR.sup.6, --N.dbd.NHCONH.sub.2, --N.dbd.NHCOCONH.sub.2, (H, OH), (H, --OR.sup.6), (H, --OCOR.sup.6), (H, OSO.sub.2 R.sup.6) or --E--(CH.sub.2).sub.n1 --G--, wherein n.sub.1 is 1 to 5, and E and G are O, S or N, and are joined to the same carbon to form a cyclic structure;
R.sup.5 is H, lower alkyl, or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl;
R.sup.6 is lower alkyl or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl;
R.sup.7, R.sup.8 and R.sup.9 are independently selected from the group consisting of H, lower alkyl, aryl, and aralkyl; and
n is 0-5.
R and R.sup.2 are halo;
R.sup.1 and R.sup.3 are H and halo, provided that at least one of R.sup.1 and R.sup.3 is H;
X is N, CH or C, when the double bond is present at the C-11 position;
R.sup.4 is=O, --NHOH, --N.dbd.NHR.sup.6, --N.dbd.NHSO.sub.2 R.sup.6, --N.dbd.NHCOR.sup.6, --N.dbd.NHCONH.sub.2, --N.dbd.NHCOCONH.sub.2, (H, OH), (H, --OR.sup.6), (H, --OCOR.sup.6), (H, OSO.sub.2 R.sup.6) or --E--(CH.sub.2).sub.n1 --G--, wherein n.sub.1 is 1 to 5, and E and G are O, S or N, and are joined to the same carbon to form a cyclic structure;
R.sup.5 is H, lower alkyl, or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl;
R.sup.6 is lower alkyl or optionally substituted aryl, heteroaryl, aralkyl, heteroaralkyl or heterocycloalkyl-alkyl;
R.sup.7, R.sup.8 and R.sup.9 are independently selected from the group consisting of H, lower alkyl, aryl, and aralkyl; and
n is 0-5.