255064-10-9Relevant academic research and scientific papers
FUSED IMIDAZOLE COMPOUNDS
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Page/Page column 102, (2015/09/23)
The present invention provides compounds represented by formula (I), pharmaceutically acceptable salts thereof, N-oxides thereof, solvates thereof or prodrugs thereof (wherein the characters are as defined in the description). The compounds represented by formula (I) have affinity and selectivity for the gamma-aminobutyric acid A receptor subunit alpha 5 (GABAA α5) and act as GABAA α5 negative allosteric modulators (GABAA α5 NAM), so that they are useful in the prevention and/or treatment of diseases which are related to the GABAA α5 such as Alzheimer's disease.
SERINE/THREONINE PAK1 INHIBITORS
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Page/Page column 130, (2013/03/26)
Compounds having the formula I wherein A, Z, R1a, R1b, R2, R3, R4, R5, R6, R7, R9, R10, Ra, Rb and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
Maximizing lipophilic efficiency: The use of Free-Wilson analysis in the design of inhibitors of acetyl-CoA carboxylase
Freeman-Cook, Kevin D.,Amor, Paul,Bader, Scott,Buzon, Leanne M.,Coffey, Steven B.,Corbett, Jeffrey W.,Dirico, Kenneth J.,Doran, Shawn D.,Elliott, Richard L.,Esler, William,Guzman-Perez, Angel,Henegar, Kevin E.,Houser, Janet A.,Jones, Christopher S.,Limberakis, Chris,Loomis, Katherine,McPherson, Kirk,Murdande, Sharad,Nelson, Kendra L.,Phillion, Dennis,Pierce, Betsy S.,Song, Wei,Sugarman, Eliot,Tapley, Susan,Tu, Meihua,Zhao, Zhengrong
supporting information; experimental part, p. 935 - 942 (2012/03/11)
This paper describes the design and synthesis of a novel series of dual inhibitors of acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2). Key findings include the discovery of an initial lead that was modestly potent and subsequent medicinal chemistry optimization with a focus on lipophilic efficiency (LipE) to balance overall druglike properties. Free-Wilson methodology provided a clear breakdown of the contributions of specific structural elements to the overall LipE, a rationale for prioritization of virtual compounds for synthesis, and a highly successful prediction of the LipE of the resulting analogues. Further preclinical assays, including in vivo malonyl-CoA reduction in both rat liver (ACC1) and rat muscle (ACC2), identified an advanced analogue that progressed to regulatory toxicity studies.
OXADIAZOLE FUSED HETEROCYCLIC DERIVATIVES USEFUL FOR THE TREATMENT OF MULTIPLE SCLEROSIS
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Page/Page column 51, (2010/08/05)
The invention provides compounds of Formula (I) for the treatment of multiple sclerosis and other diseases.
Benzimidazole derivatives. 2. Synthesis and structure-activity relationships of new azabicyclic benzimidazole-4-carboxylic acid derivatives with affinity for serotoninergic 5-HT3 receptors
López-Rodríguez, María L.,Benhamú, Bellinda,Morcillo, M. José,Tejada, Ignacio D.,Orensanz, Luis,Alfaro, M. José,Martín, M. Isabel
, p. 5020 - 5028 (2007/10/03)
A new series of azabicyclic benzimidazole-4-carboxamides 2-21 and - carboxylates 22-30 were synthesized and evaluated for binding affinity at serotoninergic 5-HT3 and 5-HT4 receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT3 binding site and low to no significant affinity for the 5-HT4 receptor. SAR observations indicated that a halogen atom at the 6-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT3 affinity and 5-HT3/5-HT4 selectivity, as well as no substitution in this ring. (S)-(-)-N-(Quinuclidin-3-yl)benzimidazole-4- carboxamides 2, 8, and 14 bound at central 5-HT3 sites with high affinity (K(i) = 2.6, 0.13, and 1.7 nM, respectively) and excellent selectivity over serotonin 5-HT4 and 5-HT(1A) receptors (K(i) > 1000-10000 nM). Furthermore, these new 5-HT3 receptor ligands were pharmacologically characterized as potent and selective 5-HT3 antagonists in the isolated guinea pig ileum (pA2 = 9.6, 9.9, and 9.1, respectively).
