136564-75-5

Upstream product

• 136564-74-4 methyl (R,S)-3-methoxy-4-<<1-methyl-5-<(2-methyl-4,4,4-trifluorobutyl)carbamoyl>indol-3-yl>methyl>benzoate 
• 156040-10-7 (R,S)-4,4,4-trifluoro-2-methylbutanamine 
• 143484-00-8 ethyl 2-methyl-4,4,4-trifluorobutanoate 
• 136564-77-7 (R,S)-4,4,4-trifluoro-2-methylbutanamide 
• 99783-23-0 4,4,4-trifluoro-2-methylbutanoic acid 
• 136564-73-3 methyl 4-<<5-carboxy-1-methylindol-3-yl>methyl>-3-methoxybenzoate 

Relevant academic research and scientific papers

Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-indolecarboxamides: Identification of 4--1-methylindol-3-yl>methyl>-3-methoxy-N-benzamide, ...

The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4--1-methylindol-3-yl>methyl>-3-methoxy-N-benzamide (38p, ZENECA ZD 3523), which has been chosen for clinical evaluation.This compound exhibited a Ki of 0.42 nM for displacement of LTD4 on guinea pig lung membranes, a pKB of 10.13 +/- 0.14 versus LTE4 on guinea pig trachea, and an oral ED50 of 1.14 μmol/kg opposite LTD4-induced bronchoconstriction in guinea pigs.The R enantiomer was found to be modestly more potent than the S enantiomer 38o.Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity.Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist.The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99percent enantiomeric purity.

Carbamoyl derivatives

The present invention concerns novel carbamoyl derivatives of formula I, set out herein, which antagonize the pharmacological actions of one or more of the arachidonic acid metabolites known as leukotrienes, making them useful whenever such antagonism is desired, such as in the treatment of those diseases in which leukotrienes are implicated, for example, in the treatment of allergic or inflammatory diseases, or of endotoxic or traumatic shock conditions. The invention also provides pharmaceutical compositions containing the novel derivatives for use in such treatments, methods for their use and processes and intermediates for the manufacture of the novel derivatives.