Details

Autor(en) / Beteiligte

• Harrison, Timothy
• Owens, Andrew P
• Williams, Brian J
• Swain, Christopher J
• Williams, Angela
• Carlson, Emma J
• Rycroft, Wayne
• Tattersall, F. David
• Cascieri, Margaret A
• Chicchi, Gary G
• Sadowski, Sharon
• Rupniak, Nadia M. J
• Hargreaves, Richard J

Titel

An Orally Active, Water-Soluble Neurokinin-1 Receptor Antagonist Suitable for Both Intravenous and Oral Clinical Administration

Ist Teil von

• Journal of medicinal chemistry, 2001-11, Vol.44 (24), p.4296-4299

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 1-(5-{[(2R,3S)-2-({(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholin-4-yl]methyl}-2H-1,2,3-triazol-4-yl)-N, N-dimethylmethanamine hydrochloride 3 is a high affinity, orally active, h-NK1 receptor antagonist with a long central duration of action and a solubility in water of >100 mg/mL. The construction of the 5-dimethylaminomethyl 1,2,3-triazol-4-yl unit, which incorporates the solubilizing group of 3, was accomplished by thermal rearrangement of a propargylic azide in the presence of dimethylamine. Compound 3 is highly effective in pre-clinical tests that are relevant to clinical efficacy in emesis and depression.