Antimigraine preparations

Antimigraine preparations (Dihydroergo-tamine, Ergotamine, Methysergide) in N02C... 

Esters of tropine have a venerable place in medicinal chemistry. One such compound, cocaine, the object of some current interest, was the natural product lead which led eventually to most of today s local anesthetics. A distantly related analogue is prepared by reaction of tropine (132) with 3,5-dimethylbenzoyl chloride. This leads to an ester structurally related to another ]ii ominent natural product, atropine (133). The product, tropanaerin (134), is described as an iinti.serotonergic agent intended for antimigraine use [34]. 

The Larock synthesis was used by Chen and co-workers to synthesize the 5-(triazolyl-methyl)tryptamme MK-0462, a potent 5-HTjn receptor agonist, as well as a metabohte [366], Larock employed his methodology to prepare tetrahydroindoles [367], and Maassarani used this method for the synthesis of /V-(2-pyridyl)indoles [368]. The latter study features the isolation of cyclopalladated Y-phenyl-2-pyridylammes. Rosso and coworkers have employed this method for the industrial-scale synthesis of an antimigraine drug candidate 331. In this paper removal of spent palladium was best effected by trimer-captotriazine (332) although many techniques were explored [369]. 

In a similar manner, another antimigraine drug candidate 1 has been prepared using a silylalkyne [86]. Here it was found that 2,4,6-trimercapto-s-triazine provides a very useful way to remove residual palladium. A number of tryptophan analogues have been prepared using this same silylalkyne chemistry, followed by protodesilylation [87-93] (Eq.43). 

Zolmitriptan [139264-17-8], antimigraine agent, 5-HT,D-agonist, 236. Intermediates in various synthetic routes to Zolmitriptan are prepared with phosgene, phosgene equivalents, or phosgene derivatives [170, 171]. 

Structurally closely related to LSD, Lisuride (226) is a compound having a 3,3-dimethylureido substituent, at die 9-position of the ergoline skeleton, and was first prepared in 1960 as a dopamine Dj-receptor agonist (98). Lisuride, as its acid maleate, is commercially available under Ae names of Cuvalit, Dopergin, Eunal, or Lysenyl, and is used clinically as an antimigraine and also as a prolactin inhibitor. The pharmacological activi and toxicity of lisuride were... 

CGRP Receptors Antagonist (Antimigraine Drugs) Enzymatic Preparation of (R)-2-amino-3-(7-methyi-l H-indazoi-5-yi)Propanoic Acid... 

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