- N-Desmethyltriptans: One pot efficient synthesis of N-methyl-2-5- [substituted- 1H- indole-3-yl]ethanamines
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A straightforward and highly improved method to synthesize N-methyl-2-[5-[substituted-lH-indole-3-yl]ethanamines 4-6, which are the metabolites of tryptans 1-3, is reported. The significance of the process is its simplicity and efficiency in isolating the N- desmethyltriptans derivatives as a free base.
- Mittapelli, Vasantha,Ray, Puma Chandra,Chauhan, Yogendra Kumar,Datta, Debashish
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experimental part
p. 590 - 594
(2010/01/06)
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- Synthesis and characterization of potential impurities of the antimigraine drug, rizatriptan benzoate
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Rizatriptan benzoate is a recently developed antimigraine drug used for the treatment of migraines and severe headaches. In the synthesis of rizatriptan benzoate in bulk,various impurities are formed. The present work details the development of a simple a
- Sarma, P. Seetharama,Rao, C. Nageswar,Surayanarayana,Reddy, Padi Pratap,Khalilluah,Praveen, Cherukupally
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p. 603 - 612
(2008/04/12)
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- 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
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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.
- Street,Baker,Davey,Guiblin,Jelley,Reeve,Routledge,Sternfeld,Watt,Beer,Middlemiss,Noble,Stanton,Scholey,Hargreaves,Sohal,Graham,Matassa
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p. 1799 - 1810
(2007/10/02)
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