| 主权项 |
1. A method for inhibiting the proteolytic activity of a post-proline-cleaving enzyme, wherein said enzyme is a mammalian dipeptidyl peptidase IV (DPP IV), comprising contacting said enzyme with an effective amount of a compound represented by: or a pharmaceutically acceptable salt thereof; wherein A represents a 4-8 membered heterocycle including the N and the Cα carbon; R1 represents a C-terminally linked amino acid residue or amino acid analog, wherein the bond between R1 and N is a thioxamide bond; R2 is absent or represents one or more substitutions to the ring A, each of which is independently a halogen, lower alkyl, lower alkenyl, lower alkynyl, carbonyl, carboxyl, ester, formate, ketone, thiocarbonyl, thioester, thioacetate, thioformate, amino, acylamino, amido, nitro, sulfate, sulfonate, sulfonamido, —(CH2)m—R7, —(CH2)m—OH, —(CH2)m—O-lower alkyl, —(CH2)m—O-lower alkenyl, —(CH2)n—O—(CH2)m—R7, —(CH2)m—SH, —(CH2)m—S-lower alkyl, —(CH2)m—S-lower alkenyl, or —(CH2)n—S—(CH2)m—R7, azido, cyano, isocyanato, thiocyanato, isothiocyanato, cyanato,or —C≡C—R8;
R3 represents hydrogen or a halogen, lower alkyl, lower alkenyl, lower alkynyl, carbonyl, thiocarbonyl, amino, acylamino, amido, nitro, sulfate, sulfonate, a sulfonamido, —(CH2)m—R7, —(CH2)m—OH, —(CH2)m—O-lower alkyl, —(CH2)m—O-lower alkenyl, —(CH2)n—O—(CH2)m—R7, —(CH2)m—SH, —(CH2)m—S-lower alkyl, —(CH2)m—S-lower alkenyl, or —(CH2)n—S—(CH2)m—R7, azido, cyano, isocyanato, thiocyanato, isothiocyanato, cyanato,or —C≡C—R8; R7 represents, for each occurrence, a substituted or unsubstituted aryl, aralkyl, cycloalkyl, cycloalkenyl, or heterocycle; R8 represents hydrogen, —CH3, or —(CH2)n—CH3; Y1 and Y2, independently, are OH, or a group capable of being hydrolyzed to a hydroxyl group, or Y1 and Y2 are connected via a ring having from 5 to 8 atoms in the ring structure which is capable of being hydrolyzed to two hydroxyl groups; m is zero or an integer in the range of 1 to 8; and n is an integer in the range of 1 to 8. |
