2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1-phosphate (S1P) receptor agonists.
A series of 2,5-cis-disubstituted pyrrolidines were synthesized and evaluated as S1P receptor agonists. Compounds 15-21 were identified with good selectivity over S1P3 which lowered circulating lymphocytes after oral administration in mice.
Department of Medical Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. vince_colandrea@merck.com
Vincent J
VJ
Colandrea
Irene E
IE
Legiec
Pei
P
Huo
Lin
L
Yan
Jeffrey J
JJ
Hale
Sander G
SG
Mills
James
J
Bergstrom
Deborah
D
Card
Gary
G
Chebret
Richard
R
Hajdu
Carol Ann
CA
Keohane
James A
JA
Milligan
Mark J
MJ
Rosenbach
Gan-Ju
GJ
Shei
Suzanne M
SM
Mandala
D000284:Administration, Oral; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry*; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D011759:Pyrrolidines; D049349:Receptors, Lysosphingolipid; C032519:pyrrolidine