Results 281 to 290 of about 107,657 (326)

SAGE-718: A First-in-Class N-Methyl-d-Aspartate Receptor Positive Allosteric Modulator for the Potential Treatment of Cognitive Impairment.

Journal of Medicinal Chemistry, 2022
N-Methyl-d-aspartate receptor (NMDAR) positive allosteric modulators (PAMs) have received increased interest as a powerful mechanism of action to provide relief as therapies for CNS disorders.
M. Hill, M. Blanco, F. Salituro, Zhu Bai, Jacob T. Beckley, M. Ackley, Jing Dai, James J. Doherty, B. Harrison, E. Hoffmann, T. Kazdoba, David Lanzetta, Michael Lewis, M. Quirk, A. Robichaud   +14 more
semanticscholar   +1 more source

Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)

Bioorganic and Medicinal Chemistry Letters, 2009
This Letter describes the synthesis and SAR of the novel positive allosteric modulator, VU0155041, a compound that has shown in vivo efficacy in rodent models of Parkinson's disease.
Kari A Johnson, Patrick R Gentry, Colleen M Niswender   +2 more
exaly   +2 more sources

Fused heterocyclic M1 positive allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2011
Fused aromatics such as naphthalene were identified as highly potent and CNS penetrant M(1) positive allosteric modulators during an SAR study to replace the phenyl B-ring linkage.
Scott D, Kuduk, Christina N, Di Marco, Victoria, Cofre, William J, Ray, Lei, Ma, Marion, Wittmann, Matthew A, Seager, Kenneth A, Koeplinger, Charles D, Thompson, George D, Hartman, Mark T, Bilodeau   +10 more
openaire   +2 more sources

Substrate-selective positive allosteric modulation of PTPRD’s phosphatase by flavonols

Biochemical Pharmacology, 2022
The receptor type protein tyrosine phosphatase D (PTPRD) is expressed by neurons and implicated in interesting phenotypes that include reward from addictive substances, restless leg syndrome and neurofibrillary tangle densities in Alzheimer's disease (AD-NFTs).
Ian M. Henderson, Carlissa Marez, Karol Dokladny, Jane Smoake, Maria Martinez, David Johnson, George R. Uhl   +6 more
openaire   +2 more sources

N-Heterocyclic derived M1 positive allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2010
Replacement of a phenyl ring with N-linked heterocycles in a series of quinolone carboxylic acid M1 positive allosteric modulators was investigated. In particular, a pyrazole derivative exhibited improvements in potency, free fraction, and CNS exposure.
Scott D, Kuduk, Christina N, Di Marco, Victoria, Cofre, Daniel R, Pitts, William J, Ray, Lei, Ma, Marion, Wittmann, Lone, Veng, Matthew A, Seager, Kenneth, Koeplinger, Charles D, Thompson, George D, Hartman, Mark T, Bilodeau   +12 more
openaire   +2 more sources

Novel bivalent positive allosteric modulators of AMPA receptor

Doklady Biochemistry and Biophysics, 2015
A positive allosteric modulator of AMPA receptors has been designed using computer-aided molecular modeling techniques. It possessed a record high experimentally confirmed potency in the picomolar concentration range and belongs to a new type of bivalent AMPA receptor ligands containing bicyclo[3.3.1]nonane scaffold. The suggested structure could serve
M I, Lavrov, V V, Grigor'ev, S O, Bachurin, V A, Palyulin, N S, Zefirov   +4 more
openaire   +2 more sources

Positive Allosteric Modulation of the Mu Opioid Receptor

The FASEB Journal, 2022
Opioid therapeutics, such as morphine, that act at the mu‐opioid receptor (MOR) are the clinical standard for patients struggling to manage symptoms associated with pain. It is widely understood that although opioids are effective at treating pain, their use leads to the development of severe adverse effects, such as constipation, addiction, and ...
Kelsey Kochan, John Traynor
openaire   +1 more source

Synthesis and Pharmacological Characterization of 2-(2,6-dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a potent, subtype selective, and orally available positive allosteric modulator of the human dopamine D1

Journal of Medicinal Chemistry, 2019
Clinical development of catechol-based orthosteric agonists of the dopamine D1 receptor has thus far been unsuccessful due to multiple challenges. To address these issues, we identified LY3154207 (3) as a novel, potent, and subtype selective D1 positive ...
J. Hao, J. Beck, Johm M Schaus, J. Krushinski, Qi Chen, C. D. Beadle, Paloma Vidal, Matt R. Reinhard, Bruce A. Dressman, S. Massey, S. Boulet, M. Cohen, B. Watson, D. Tupper, K. Gardinier, J. Myers, A. Johansson, J. Richardson, D. Richards, E. Hembre, D. Remick, David A Coates, R. Bhardwaj, B. Diseroad, D. Bender, G. Stephenson, C. Wolfangel, Nuria Díaz, B. Getman, Xushan Wang, B. Heinz, J. Cramer, Xin Zhou, Deanna L. Maren, J. Falcone, R. Wright, S. Mitchell, Guy Carter, Charles R. Yang, R. F. Bruns, K. Svensson   +40 more
semanticscholar   +1 more source

Positive Allosteric Modulator of the Human 5-HT2C Receptor

Molecular Pharmacology, 2003
The human 5-hydroxytryptamine-2C (5-HT2C) receptor has been the target of potential anxiolytics and antiobesity drugs, and its positive allosteric modulator was discovered to be l-threo-alpha-d-galacto-octopyranoside, methyl-7-chloro-6,7,8-trideoxy-6-[[(4-undecyl-2-piperidinyl)carbonyl]amino]-1-thiomonohydrochloride (2S-cis) (PNU-69176E).
Wha Bin, Im, Christopher L, Chio, Glen L, Alberts, Dac M, Dinh   +3 more
openaire   +2 more sources

Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator

, 2019
Drugs targeting the orthosteric, primary binding site of G protein–coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically.
Xiangyu Liu, A. Masoudi, Alem W. Kahsai, Li-Yin Huang, Biswaranjan Pani, K. Hirata, Seungkirl Ahn, R. Lefkowitz, B. Kobilka   +8 more
semanticscholar   +1 more source