144235-64-3Relevant academic research and scientific papers
NOVEL PROCESS
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Page/Page column 12-13, (2009/01/24)
The present invention relates to a novel process for the preparation of rizatriptan and its pharmaceutically acceptable salts. It provides a novel process for the preparation of highly pure rizatriptan, which can be easily adopted for commercial production with a high degree of consistency in purity and yield. Subsequently the rizatriptan base preparedcan be converted into any suitable pharmaceutically acceptable salt, such as the oxalate, succinate or benzoate salt,for dosage form preparation. The present invention also provides a composition comprising rizatriptan useful for the manufacture of a medicament for the treatment or prevention of migraine.
Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol- 1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: Potent agonists for 5- HT(1D) receptors
Street,Baker,Davey,Guiblin,Jelley,Reeve,Routledge,Sternfeld,Watt,Beer,Middlemiss,Noble,Stanton,Scholey,Hargreaves,Sohal,Graham,Matassa
, p. 1799 - 1810 (2007/10/02)
The synthesis and the 5-HT receptor activity of a novel series of N,N- dimethyltryptamines substituted in the 5-position with an imidazole, triazole, or tetrazole ring are described. The objective of this work was to identify potent and selective 5-HT(1D) receptor agonists with high oral bioavailability and low central nervous system penetration. Compounds have been prepared in which the azole ring is attached through either nitrogen or carbon to the indole. Conjugated and methylene-bridged derivatives have been studied (n = 0 or 1). Substitution of the azole ring has been explored either α or β to the point of attachment to indole. In a series of N-linked azoles (X = N), simple unsubstituted compounds have high affinity and selectivity for 5-HT(1D) receptors. It is proposed that for good affinity and selectivity a hydrogen bond acceptor interaction with the 5-HT(1D) receptor, through a β-nitrogen in the azole ring, is required. In a series of C-linked triazoles and tetrazoles (X = C), optimal affinity and selectivity for the 5-HT(1D) receptor was observed when the azole ring is substituted at the 1-position with a methyl or ethyl group. This study has led to the discovery of the 1,2,4-triazole 10a (MK-462) as a potent and selective 5-HT(1D) receptor agonist which has high oral bioavailability and rapid oral absorption. The in vitro activity and the preliminary pharmacokinetics of compounds in this series are presented.
