35982-98-0Relevant academic research and scientific papers
Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type i positive allosteric modulators of α7 nicotinic acetylcholine receptors
Hogenkamp, Derk J.,Ford-Hutchinson, Thomas A.,Li, Wen-Yen,Whittemore, Edward R.,Yoshimura, Ryan F.,Tran, Minhtam B.,Johnstone, Timothy B. C.,Bascom, Gavin D.,Rollins, Hannah,Lu, Lena,Gee, Kelvin W.
, p. 8352 - 8365 (2013/12/04)
A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of α7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to be type I positive allosteric modulators (PAMs) of human α7 nAChRs expressed in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the identification of compound 7v as a potent and efficacious type I PAM with maximum modulation of a nicotine EC 5 response of 1200% and EC50 = 0.18 μM. Compound 7z was active in reversing the effect of scopolamine in the novel object recognition (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 μmol/kg). This effect was blocked by the selective α7 nAChR antagonist methyllycaconitine (MLA). These compounds are potent type I positive allosteric modulators of α7 nAChRs that may have therapeutic value in restoring impaired sensory gating and cognitive deficits in schizophrenia and Alzheimer's disease.
Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors
Zhang, Zhichao,Liu, Chengwu,Li, Xiangqian,Song, Ting,Wu, Zhiyong,Liang, Xiaomeng,Zhao, Yan,Shen, Xiaoyun,Chen, Hongbo
, p. 410 - 420 (2013/04/10)
We have previously reported a nanomolar inhibitor of antiapoptotic Mcl-1 protein, 3-thiomorpholin-8-oxo-8H-acenaphtho [1,2-b] pyrrole-9-carbonitrile (S1). S1 plays its function by binding to the BH3 groove of Mcl-1. Basing on this spacial structural characteristic, we developed a novel class of Mcl-1 inhibitor using fragment-based drug discovery approach. By dissecting S1, we identified the compound 4 with a 2-hydroxypyridine core as the starting fragment. In the following molecular growth, we used the ligand efficiency evaluation and fit quality score to assess the fragments. A novel potent compound, N-benzyl-5-(4-isopropylthiophenol)-2-hydroxyl nicotinamide (12c), which binds Mcl-1 with an IC50 value of 54 nM was obtained. Compound 12c demonstrated a better aqueous solubility than S1.
Dihydropyridazinones, pyridazinones and related compounds as fungicides
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, (2008/06/13)
This invention relates to substituted dihydropyridazinones, pyridazinones and related compounds, of the formula STR1 wherein A, Q, D and R1 are as defined within, compositions containing these compounds and methods of controlling agricultural and mammalian fungal diseases.
New synthetic routes to 3-, 5-, and 6-aryl-2-chloropyridines
Church,Trust,Albright,Powell
, p. 3750 - 3758 (2007/10/02)
The efficient synthesis of 3-, 5-, and 6-aryl-2-chloropyridines via the facile preparation of 5-(dimethylamino)aryl-substituted pentadienyl nitriles and cyclization with hydrochloric acid is described. This approach allows for the introduction of other electron-withdrawing substituents on the pyridine ring as well as the preparation of the desired unsubstituted arylpyridines. Some differences in the rates of cyclization of the pentadienyl nitriles as well as the yields of chloropyridines were observed that depended on the position and degree of substitution in the aryl substituent. The arylpentadienyl nitriles 5 and 6 could also be converted directly into the corresponding 2-aminopyridines.
1-Benzoyl-3-(arylphyridyl)urea compounds
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, (2008/06/13)
The present invention is directed to 1-benzoyl-3-(arylpyridyl)urea compounds useful as insecticides.
