Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 4. Effect of various side-chain substituents on therapeutic activity against anticholinesterase intoxication
摘要:
A series of quaternary salt derivatives of 2-[(hydroxyimino)methyl]-1-methylimidazole incorporating various side chains bearing ether, silyl, nitrile, ester, halogen, nitro, sulfone, amino, or aminosulfonyl substituents was prepared and evaluated in vivo for the treatment of anticholinesterase intoxication. Test results in the mouse revealed that the type and location of the side-chain substituent both have a significant influence on the toxicity and antidotal effectiveness of the compounds. Some of the more active examples represent the most potent therapeutics to date against intoxication by the powerful cholinesterase inhibitors soman and tabun. Significantly, the antidotal effectiveness of the compounds was not dependent on the inhibiting agent nor was there any correlation between in vivo efficacy and in vitro reactivation of ethyl (4-nitrophenyl)methylphosphonate inhibited human acetylcholinesterase. These observations suggested that the main mode of antidotal protection by the compounds is something other than enzyme reactivation.
[EN] FUSED BICYCLIC COMPOUNDS AND USE THEREOF AS PI3K INHIBITORS<br/>[FR] COMPOSÉS BICYCLIQUES FUSIONNÉS ET UTILISATIONS DE CEUX-CI COMME INHIBITEURS DE P13K
申请人:MERCK SERONO SA
公开号:WO2009133127A1
公开(公告)日:2009-11-05
The invention relates to compounds of formula (I), for the regulation of phosphoinositides 3-kinases activity and related diseases.
这项发明涉及到式(I)的化合物,用于调节磷脂酰肌醇3-激酶的活性和相关疾病。
[EN] BENZIMIDAZOLE DERIVATIVES, COMPOSITIONS CONTAINING THEM, PREPARATION THEREOF AND USES THEREOF<br/>[FR] DERIVES DE BENZIMIDAZOLE, COMPOSITIONS LES CONTENANT, PREPARATION DE CES COMPOSITIONS ET UTILISATIONS CORRESPONDANTES
申请人:ASTRAZENECA AB
公开号:WO2005030761A1
公开(公告)日:2005-04-07
Compounds of Formula (I) or pharmaceutically acceptable salts thereof; wherein R1, R2, R3, R4, n and Ar are as defined in the specification as well as salts and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.