| 摘要 |
The invention provides hydrazine derivatives of formula (I) wherein R1 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2 is an acyl group derived from an .alpha.-, .bet a.- , .gamma.- or .delta.-(amino, hydroxy or thiol) carboxylic acid in which the amino, hydroxy or thiol group is optionally lower alkylated or the amino gro up is optionally acylated, sulphonylated or amidated and in which any functiona l group present in a side-chain is optionally protected, or a group of the formula Het(CH2)mCO; R3 is hydrogen, lower alkyl, halo-lower alkyl, cyano- lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alky l, lower alkoxycarbonyl-lower alkyl, lower cycloalkyl-lower alkyl, aryl-lower alkyl, heterocyclyl-lower alkyl, heterocyclylcarbonyl-lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, aryl-lower alkenyl, aryl or heterocyclyl; R4 is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl or a grouping of the formula X-aryl, X-heteroaryl or (CH2)n-CH=CR5R6; R5 and R6 together are lower alkylene in which one CH2 grou p is optionally replaced by a hetero atom; Het is heterocyclyl; X is a spacer group; m is 0, 1, 2, 3 or 4; and n is 1 or 2; and their pharmaceutically acceptable salts inhibit therelease of tumour necrosis factor alpha (TNF- .alpha.) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respirato ry diseases, tumours, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.
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