177945-99-2

Upstream product

• 78643-42-2 5-bromopentanal dimethyl acetal 
• 104-04-1 N-(4-Nitrophenyl)acetamide 
• 122-80-5 N-acetyl-p-phenylenediamine 
• 177947-84-1 1-{3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl}piperidin-4-one 
• 177947-82-9 1-{3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl}piperidin-4-ol 
• 177947-81-8 5-(4-hydroxypiperidin-1-yl)pentanal dimethyl acetal 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 63630-08-0 N-[4-(2-aminoethyl)phenyl]acetamide 

Relevant academic research and scientific papers

PALLADIUM CATALYZED INDOLIZATION

We have found that 2-unsubstituted indoles of structural formula (IV) can be cost-effectively synthesized in high yield by the palladium-catalyzed coupling/ring closure of a 2-halo or 2-trifluoromethylsulfonyloxy aniline (I) and an acyl silane derivative (II), followed by deprotection of the silyl protecting groups. The process of the present invention is particularly useful to form indoles containing acid-labile substituents such as triazole, acetyl, ketal, cyano, and carbamate, or indoles having a good leaving group in the benzyl position. The advantages of the present process are that it does not require the use of triphenyl phosphine or tetrabutyl ammonium chloride or lithium chloride. When applied to 5-triazolyl substituted indoles, the present process also eliminates the tendency of triazolyl polymerization in the Fischer indole synthesis. Still further, the present invention is also directed to the novel intermediates of structural formulae (V) and (VI).

3-[3-(piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists

Several 5-HT(ID/1B) receptor agonists are now entering the marketplace as treatments for migraine. This paper describes the development of selective h5-HT(1D)receptor agonists as potential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80 (L-772,405), a high- affinity h5-HT(1D) receptor full agonist having 170-fold selectivity for h5- HT(1D) receptors over h5-HT(1B) receptors. L-772,405 also shows very good selectivity over a range of other serotonin and nonserotonin receptors and has excellent bioavailability following subcutaneous administration in rats. It therefore constitutes a valuable tool to delineate the role of h5-HT(1D) receptors in migraine. Molecular modeling and physical properties have been utilized to postulate the binding conformation of these compounds in the receptor cavity.

Azetidine, pyrrolidine and piperidine derivatives

A class of substituted azetidine, pyrrolidine and piperidine derivatives are selective agonists of 5-HT1 -like receptors, being potent agonists of the human 5-HT1Dα receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT1Dα receptor subtype relative to the 5-HT1Dβ subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.