2-CYANO-3,5-DIHYDROXYHEX-2-ENECARBOXAMIDE DERIVATIVE

PROBLEM TO BE SOLVED: To obtain a new 2-cyano-3,5-dihydroxyhex-2-enecarboxamide derivative useful as a medicine for preventing and treating disease and damage including the increase of degradation of connective tissue and cartilage. SOLUTION: This 2-cyano-3,5-dihydroxyhex-2enecarboxamide derivative is represented by formula I [R is H or a 1-4C alkyl; R is a 1-12C alkyl, a 2-12C alkenyl, etc.; R is CF3 , OCF3 , etc.; R is a 1-4C alkyl, a halogen or H; (n) is 1-4], e.g. N-(phenyl)-2-cyano-3,5-dihydroxy-5-methylhex-5-enecarboxamide. The compound of formula I is obtained by treating a (substituted) 5- methylisoxazole-3-carboxamide or anilide with an organic metal base, e.g. butyl lithium at a low temperature, reacting the treated material with an electrophilic reagent such as an aldehyde and a ketone and acidifying and extracting the product. The compound directly stimulates proteoglycan production of cartilage cell or inhibits the increase of degradation of the proteoglycan induced by interleukin-1.