- PROGRANULIN MODULATORS AND METHODS OF USING THE SAME
-
Provided herein are compounds of formula (I) that modulate progranulin and methods of using the compounds in progranulin- associated disorders, such as Frontotemperal lobe dementia (FTLD).
- -
-
Page/Page column 0109; 0112
(2021/04/30)
-
- Discovery of quinuclidine modulators of cellular progranulin
-
Phenotypic screening of an annotated small molecule library identified the quinuclidine tetrahydroisoquinoline solifenacin (1) as a robust enhancer of progranulin secretion with single digit micromolar potency in a murine microglial (BV-2) cell line. Subsequent SAR development led to the identification of 29 with a 38-fold decrease in muscarinic receptor antagonist activity and a 10-fold improvement in BV-2 potency.
- Burnett, Duane A.,Chen, Angela Y.-P.,Koenig, Gerhard,Lanter, James C.,Williamson, Toni,Blain, Jean-Fran?ois
-
supporting information
(2021/06/30)
-
- Diprotonative stabilization of ring-opened carbocationic intermediates: conversion of tetrahydroisoquinoline to triarylmethanes
-
Superacid-promoted conversion of tetrahydroisoquinolines to triarylmethanes via tandem reactions of C-N bond scission, Friedel-Crafts alkylation, C-O bond scission, and electrophilic aromatic amidation was developed. Dication formation was important for stabilizing the ring-opened carbocationic intermediate, which is a new role for diprotonation in reaction mechanisms. This journal is
- Kurouchi, Hiroaki
-
supporting information
p. 8313 - 8316
(2020/08/17)
-
- PROGRANULIN MODULATORS AND METHODS OF USING THE SAME
-
Provided herein are compounds that modulate progranulin and methods of using the compounds in progranulin-associated disorders, such as Frontotemporal dementia (FTD).
- -
-
Paragraph 0094
(2020/12/30)
-
- Phencyclidine-like Effects of Tetrahydroisoquinolines and Related Compounds
-
A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothienopyridines, and related compounds were evaluated for their ability to inhibit binding of -1--N-allylnormetazocine to phencyclidine (PCP) and ? receptors, respectively.A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia.All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.
- Gray, Nancy M.,Cheng, Brian K.,Mick, Stephen J.,Lair, Cecelia M.,Contreras, Patricia C.
-
p. 1242 - 1248
(2007/10/02)
-