TETRAHYDROFURO [3, 2 -B] PYRR0L-3-ONES AS CATHEPSIN K INHIBITORS

摘要

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; one of R<SUP>1</SUP> and R<SUP>2</SUP> is H, and the other is selected from from OR<SUP>6</SUP>, SR<SUP>6</SUP>, NR<SUP>6</SUP>R<SUP>7</SUP>, N<SUB>3</SUB>, Me, Et, CF<SUB>3</SUB>, SOR<SUP>8</SUP> and SO<SUB>2</SUB>R<SUP>8</SUP>; R<SUP>3</SUP> is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; R<SUP>4</SUP> is optionally substituted C<SUB>1-8</SUB> alkyl or optionally substituted C<SUB>3-8</SUB> cycloalkyl; R<SUP>6</SUP> and R<SUP>7</SUP> are each independently selected from H, C<SUB>1-8</SUB>-alkyl and C<SUB>3-8</SUB>-cycloalkyl, or R<SUP>6</SUP> and R<SUP>7 </SUP>are linked to form a cyclic group together with the nitrogen to which they are attached; and R<SUP>8</SUP> is C<SUB>1-8</SUB>-alkyl or C<SUB>3-8</SUB>-cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.