Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5.
Optimization of a screening hit from uHTS led to the discovery of TGR5 agonist 32, which was shown to have activity in a rodent model for diabetes.
Herbert
Mark R
MR
Department of Chemistry, Kalypsys, Inc.,10420 Wateridge Circle, San Diego, CA 92121, USA.
Siegel
Dana L
DL
Staszewski
Lena
L
Cayanan
Charmagne
C
Banerjee
Urmi
U
Dhamija
Sangeeta
S
Anderson
Jennifer
J
Fan
Amy
A
Wang
Li
L
Rix
Peter
P
Shiau
Andrew K
AK
Rao
Tadimeti S
TS
Noble
Stewart A
SA
Heyman
Richard A
RA
Bischoff
Eric
E
Guha
Mausumee
M
Kabakibi
Ayman
A
Pinkerton
Anthony B
AB
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use
C513561:Gpbar1 protein, mouse; D006912:Hydroxyquinolines; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D013876:Thiophenes; D052216:Glucagon-Like Peptide 1; C037219:quinoline