943138-46-3Relevant academic research and scientific papers
Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
Pinkerton, Anthony B.,Peddibhotla, Satyamaheshwar,Yamamoto, Fusayo,Slosky, Lauren M.,Bai, Yushi,Maloney, Patrick,Hershberger, Paul,Hedrick, Michael P.,Falter, Bekhi,Ardecky, Robert J.,Smith, Layton H.,Chung, Thomas D. Y.,Jackson, Michael R.,Caron, Marc G.,Barak, Lawrence S.
supporting information, p. 8357 - 8363 (2019/09/10)
Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give 18 (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.
SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
-
Paragraph 00436, (2016/04/26)
Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
Lead optimization of methionine aminopeptidase-2 (MetAP2) inhibitors containing sulfonamides of 5,6-disubstituted anthranilic acids
Wang, Gary T.,Mantei, Robert A.,Kawai, Megumi,Tedrow, Jason S.,Barnes, David M.,Wang, Jieyi,Zhang, Qian,Lou, Pingping,Garcia, Lora A.,Bouska, Jennifer,Yates, Melinda,Park, Chang,Judge, Russell A.,Lesniewski, Richard,Sheppard, George S.,Bell, Randy L.
, p. 2817 - 2822 (2008/02/03)
A series of aryl sulfonamides of 5,6-disubstituted anthranilic acids were identified as potent inhibitors of methionine aminopeptidase-2 (MetAP2). Small alkyl groups and 3-furyl were tolerated at the 5-position of anthranilic acid, while -OCH3, CH3, and Cl were found optimal for the 6-position. Placement of 2-aminoethoxy group at the 6-position enabled interaction with the second Mn2+ but did not result in enhancement in potency. Introduction of a tertiary amino moiety at the ortho-position of the sulfonyl phenyl ring gave reduced protein binding and improved cellular activity, but led to lower oral bioavailability.
