Structure-activity relationship studies of S1P agonists with a dihydronaphthalene scaffold.
Bioorg Med Chem Lett
; 22(1): 144-8, 2012 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-22153936
ABSTRACT
Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sphingosine
/
Lysophospholipids
/
Chemistry, Pharmaceutical
/
Receptors, Lysosphingolipid
/
Naphthalenes
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2012
Type:
Article
Affiliation country:
Japan