2-Aryl(pyrrolidin-4-yl)acetic acids are potent agonists of sphingosine-1-phosphate (S1P) receptors.
A series of 2-aryl(pyrrolidin-4-yl)acetic acids were synthesized and their biological activities were evaluated as agonists of S1P receptors. These analogs were able to induce lowering of lymphocyte counts in the peripheral blood of mice and were found to have good overall pharmacokinetic properties in rat.
Yan
Lin
L
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. lin_yan@merck.com
Budhu
Richard
R
Huo
Pei
P
Lynch
Christopher L
CL
Hale
Jeffrey J
JJ
Mills
Sander G
SG
Hajdu
Richard
R
Keohane
Carol A
CA
Rosenbach
Mark J
MJ
Milligan
James A
JA
Shei
Gan-Ju
GJ
Chrebet
Gary
G
Bergstrom
James
J
Card
Deborah
D
Mandala
Suzanne M
SM
D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018655:Lymphocyte Count; D008246:Lysophospholipids / Q000037:antagonists & inhibitors; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000085:Acetates; D008246:Lysophospholipids; D011759:Pyrrolidines; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine