81018-29-3Relevant articles and documents
Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel
Chen, Youwei,Li, Yuxin,Pan, Li,Liu, Jingbo,Wan, Yingying,Chen, Wei,Xiong, Lixia,Yang, Na,Song, Haibin,Li, Zhengming
, p. 6366 - 6379 (2015/01/09)
In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activities of title compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of title compounds showed moderate to high activities at the tested concentration. The structure-activity relationship (SAR) was discussed in detail. During synthesizing title compounds B8, C7, D1, D9 and D12, their corresponding positional isomers (B8′, C7′, D1′, D9′ and D12′) were afforded, and their structures were confirmed by 2D NMR. The calcium-imaging technique was also applied to investigate the effects of compounds B2, B10, C4 and C5 on the intracellular calcium ion concentration ([Ca2+]i), which indicated that they released stored calcium ions from endoplasmic reticulum, which denoted that some compounds are potential modulators of the insect ryanodine receptor (RyR).
Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
Hamann, Lawrence G.,Manfredi, Mark C.,Sun, Chongqing,Krystek Jr., Stanley R.,Huang, Yanting,Bi, Yingzhi,Augeri, David J.,Wang, Tammy,Zou, Yan,Betebenner, David. A.,Fura, Aberra,Seethala, Ramakrishna,Golla, Rajasree,Kuhns, Joyce E.,Lupisella, John A.,Darienzo, Celia J.,Custer, Laura L.,Price, Jennifer L.,Johnson, James M.,Biller, Scott A.,Zahler, Robert,Ostrowski, Jacek
, p. 1860 - 1864 (2008/02/04)
Pharmacokinetic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. Subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential.
