COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA AND CANCER

摘要

Formula (I): Where R<SUP>1</SUP> is an optionally substituted C<SUB>3</SUB>-C<SUB>12</SUB> hydrocarbyl group (preferably a cyclic alkyl group), an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R is a C(O)<SUB>y</SUB>R' group (preferably forming an optionally substituted C<SUB>2</SUB>-C<SUB>5</SUB> acyl group), or a S(O)<SUB>x</SUB>R' group, where y is 0 or 1 and x is 0, 1 or 2 and R' is H or an optionally substituted C<SUB>1</SUB>-C<SUB>12</SUB> alkyl group, or R' is an optionally substituted C<SUB>5</SUB>-C<SUB>12</SUB> cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R<SUP>5</SUP>, R<SUP>6</SUP>, R<SUP>7</SUP>, R<SUP>8</SUP>, R<SUP>9</SUP> and R<SUP>10</SUP> are each independently selected from H, an optionally substituted C<SUB>1</SUB>-C<SUB>12</SUB> hydrocarbyl group, including a C<SUB>5</SUB>-C<SUB>12</SUB> cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R<SUP>5</SUP> and R<SUP>6</SUP>, R<SUP>7</SUP> and R<SUP>8</SUP> or R<SUP>9</SUP> and R<SUP>10</SUP> together form a keto (C=O) group; R<SUP>N</SUP> is H, an optionally substituted C<SUB>1</SUB>-C<SUB>12</SUB> hydrocarbyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group, or an optionally substituted heteroaromatic group; A is Formula (II): a Formula (III): group, or a Formula (IV) or Formula (V) group, where Z is N, O or S; R<SUP>a</SUP> is H, a C<SUB>1</SUB>-C<SUB>12</SUB> optionally substituted hydrocarbyl group or an optionally substituted aromatic group; n is from 0 to 3; and pharmaceutically acceptable salts thereof. Compounds according to the invention are useful in one or more aspects to inhibit farnesyl transferase, or to treat malaria, neoplasia, a hyperproliferative disease state or arthritis, including rheumaroid arthritis or osteoarthritis.