5-HT1F agonists
Theories regarding the pathophysiology of migraine have been dominated since 1938 by the work of Graham and Wolff. , 39:737-63, 1938. They proposed that the cause of migraine headache was vasodilatation of extracranial vessels. This view was supported by knowledge that ergot alkaloids and sumatripta...
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| Main Authors | , |
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| Format | Patent |
| Language | English |
| Published |
24.02.2004
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| Online Access | Get full text |
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| Summary: | Theories regarding the pathophysiology of migraine have been dominated since 1938 by the work of Graham and Wolff.
, 39:737-63, 1938. They proposed that the cause of migraine headache was vasodilatation of extracranial vessels. This view was supported by knowledge that ergot alkaloids and sumatriptan, a hydrophilic 5-HT
agonist which does not cross the blood-brain barrier, contract cephalic vascular smooth muscle and are effective in the treatment of migraine. Humphrey, et al.,
., 600:587-600, 1990. Recent work by Moskowitz has shown, however, that the occurrence of migraine headaches is independent of changes in vessel diameter.
, 12:5-7, 1992.
The present invention relates to substituted furo[3,2-b]pyridine compounds of formula I: or a pharmaceutical acid addition salt thereof; where;R is E-D is C CH or CH-CH;Ris hydrogen or C-Calkyl;Ris hydrogen, halo, hydroxy, -NRR, -SR, -C(O)R, -C(O)MRR, -NRSOR, -NHC(Q)NRR, -NHC(O)OR, or -NRC(O)R;R, R, and Rare independently hydrogen, C-Calkyl, C-Calkenyl, C-Calkynyl, or -(CH)aryl; or Rand Rcombine, together with the nitrogen to which they are attached, form a pyrrolidine, piperidine, piperazine, 4-substituted piperazine, morpholine, or thiomorpholine ring;n is 0, 1, 2, 3, 4, 5, or 6; andQ is O or S.The present invention further relates to pharmaceutical. formulations containing compounds formula I and to the use of compounds of formula I for activating 5-HTreceptors, inhibiting neuronal protein extravasation, and treating and/or preventing migraine in a mammal. |
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