219614-66-1Relevant academic research and scientific papers
Compounds as inhibitor of tumor necrosis factor alpha release
-
, (2008/06/13)
The invention provides hydrazine derivatives of the formula wherein R1is lower alkyl, lower alkenyl, lower cycloalkyl, lower cycloalkyl-lower alkyl, aryl or aryl-lower alkyl; R2is an acyl group derived from an α-, β-, γ- or δ-(amino, hydroxy or thiol)carboxylic acid in which the amino, hydroxy or thiol group is optionally lower alkylated or the amino group is optionally acylated, sulphonylated or amidated and in which any functional group present in a side-chain is optionally protected, or a group of the formula Het(CH2)mCO; R3is hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, 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; R4is 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; R5and R6together are lower alkylene in which one CH2group 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 the release of tumour necrosis factor alpha (TNF-α) from cells. They can be used as medicaments, especially in the treatment of inflammatory and autoimmune diseases, osteoarthritis, respiratory diseases, tumours, cachexia, cardiovascular diseases, fever, haemorrhage and sepsis.
Practical approaches to the matrix metalloproteinase inhibitor Trocade (Ro 32-3555) and to the TNF-α converting enzyme inhibitor Ro 32-7315
Hilpert, Hans
, p. 7675 - 7683 (2007/10/03)
Stereoselective methods were found to efficiently prepare 2- and 3-substituted succinates with anti configuration. In the synthesis of Trocade 1, the hydantoinmethyl residue was introduced by alkylation of the non-chelated potassium enolate 19 with the br
