Aminoisoquinolines and aminotheinopyridine derivatives and their use as
申请人:Astra Pharmaceuticals, Ltd.
公开号:US06063789A1
公开(公告)日:2000-05-16
Compounds of formula I ##STR1## wherein R, R.sup.1, R.sup.2, and R.sup.3 and A are as defined herein, together with pharmaceutically acceptable salts, enantiomers or tautomers are useful as pharmaceuticals, particularly in the treatment of inflammatory disease.
Efficient synthesis of 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acid ethyl esters
作者:Douglas E. Murphy、Peter S. Dragovich、Benjamin K. Ayida、Thomas M. Bertolini、Lian-Sheng Li、Frank Ruebsam、Nebojsa S. Stankovic、Zhongxiang Sun、Jingjing Zhao、Yuefen Zhou
DOI:10.1016/j.tetlet.2007.11.187
日期:2008.1
boxylic acidethylesters (6-substituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acidethylesters). These compounds are shown to undergo selective alkylation at the 2-position in moderate to good yields (19–77%) to afford 2,6-disubstituted-5-hydroxy-3-oxo-2,3-dihydro-pyridazine-4-carboxylic acidethylesters (2,6-disubstituted-5-hydroxy-3(2H)-pyridazinone-4-carboxylic acidethylesters).
2,6-Disubstituted 5-hydroxy-3(2H)-pyridazinone-4-carboxylic acid ethyl esters were synthesized from α-keto esters via an efficient three-step sequence including hydrazone formation, acylation with ethyl malonyl chloride, and subsequent Dieckmann cyclization.
A novelrearrangement process involving the migration of trimethylstannanyl or trimethylsilanyl groups around the thiazole ring provides access to either 2- or 5-metallated thiazoles by tuning the reaction conditions. The proposed mechanism, based on experimental evidence, is characterized by the catalytic role of thiazole bisadducts as metal-transfer agents.
Compounds of formula I ##STR1## wherein Z, X, R, R.sub.0, R.sub.1, R.sub.2 and R.sub.3 are as defined in the description, have valuable pharmaceutical properties and are effective especially against tumors. They are prepared in a manner known per se.