Synthesis, structure-activity relationships, and biological profiles of a dihydrobenzoxathiin class of histamine H(3) receptor inverse agonists.
Bioorg Med Chem Lett
; 19(15): 4232-6, 2009 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-19520574
ABSTRACT
A series of novel dihydrobenzoxathiin derivatives was synthesized and evaluated as potent human histamine H(3) receptor inverse agonists. After systematic modification of lead 1a, the potent and selective histamine H(3) inverse agonist 1-(3-{4-[(2S,3S)-8-methoxy-3-methyl-4,4-dioxido-2,3-dihydro-1,4-benzoxathiin-2-yl]phenoxy}propyl)pyrrolidine (5k) was identified. Compound 5k showed good pharmacokinetic profiles and brain penetrability in laboratory animals. After 3mg/kg oral administration of 5k, significant elevation of brain histamine levels was observed in rats where the brain H(3) receptor was fully occupied.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxathiins
/
Chemistry, Pharmaceutical
/
Receptors, Histamine H3
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2009
Document type:
Article
Affiliation country:
Japón
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM