排序方式: 共有26条查询结果,搜索用时 15 毫秒
1.
Vu AT Campbell AN Harris HA Unwalla RJ Manas ES Mewshaw RE 《Bioorganic & medicinal chemistry letters》2007,17(14):4053-4056
A new class of estrogen receptor beta (ERbeta) ligands based on the 6H-chromeno[4,3-b]quinoline scaffold has been prepared. Several C7-substituted analogues displayed high affinity and modest selectivity for ERbeta. 相似文献
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Zhang P Kern JC Terefenko EA Fensome A Unwalla R Zhang Z Cohen J Berrodin TJ Yudt MR Winneker RC Wrobel J 《Bioorganic & medicinal chemistry》2008,16(13):6589-6600
Novel 7-aryl benzo[1,4]oxazepin-2-ones were synthesized and evaluated as non-steroidal progesterone receptor (PR) modulators. The structure activity relationship of 7-aryl benzo[1,4]oxazepinones was examined using the T47D cell alkaline phosphatase assay. A number of 7-aryl benzo[1,4]oxazepinones such as 10j and 10v demonstrated good in vitro potency (IC(50) of 10-30 nM) and selectivity (over 100-fold) at PR over other steroidal receptors such as glucocorticoid and androgen receptors (GR and AR). Several 7-aryl benzo[1,4]oxazepinones were active in the rat uterine decidualization model. In this in vivo model, compounds 10j and 10u were active at 3 mg/kg when dosed orally. 相似文献
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Ronald C. Bernotas Robert R. Singhaus David H. Kaufman John Ullrich Horace Fletcher Elaine Quinet Ponnal Nambi Rayomand Unwalla Anna Wilhelmsson Annika Goos-Nilsson Mathias Farnegardh Jay Wrobel 《Bioorganic & medicinal chemistry》2009,17(4):1663-1670
A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC50 = 1.9 nM for LXRβ and EC50 = 34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists 相似文献
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Collins MA Hudak V Bender R Fensome A Zhang P Miller L Winneker RC Zhang Z Zhu Y Cohen J Unwalla RJ Wrobel J 《Bioorganic & medicinal chemistry letters》2004,14(9):2185-2189
A series of 1,4-dihydro-2H-[d][3,1]-benzoxazin-2-one and 1,3-dihydro-[3H]-indol-2-one containing 6- or 5-, respectively, appended substituted pyrrole moieties were synthesized and evaluated for their ability to modulate the activity of the progesterone receptor (PR). Key structural changes to the pyrrole moieties of these molecules were shown to have a predictive influence as to whether the compounds behaved as PR agonists or antagonists. Compounds with the 5(')-cyano-2(')-pyrrole moiety (e.g., 32, 33, and 38) were shown to be potent PR agonists (EC(50)'s of 1.1, 1.8, and 2.8 nM, respectively). Compounds with the 5(')-nitro-2(')-pyrrole moiety (e.g., 34 and 36) were shown to be PR antagonists (IC(50)'s of 180 and 36 nM, respectively). 相似文献
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Baihua Hu Raymound Unwalla Michael Collini Elaine Quinet Irene Feingold Annika Goos-Nilsson Anna Wihelmsson Ponnal Nambi Jay Wrobel 《Bioorganic & medicinal chemistry》2009,17(10):3519-3527
A series of cinnolines/quinolines was prepared and it was found that 4-phenyl-cinnoline/quinolines with either a 2′,3′ or 2′,5′-disubstituted benzyloxy moiety or the 1-Me-7-indole methoxy moiety on the meta position of the 4-phenyl ring showed good binding selectivity for LXRβ over LXRα. The LXRβ binding selective modulators displayed good activity for inducing ABCA1 gene expression in J774 macrophage cell line and poor efficacy in the LXRα Gal4 functional assay. 26, 37 and 41 were examined for their ability to induce SREBP-1c gene expression in Huh-7 liver cell line and they were weak partial agonists. 相似文献
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Baihua Hu Ron Bernotas Rayomand Unwalla Michael Collini Elaine Quinet Irene Feingold Annika Goos-Nilsson Anna Wilhelmsson Ponnal Nambi Mark Evans Jay Wrobel 《Bioorganic & medicinal chemistry letters》2010,20(2):689-693
A series of quinoline-3-carboxamide containing sulfones was prepared and found to have good binding affinity for LXRβ and moderate binding selectivity over LXRα. The 8-Cl quinoline analog 33 with a high TPSA score, displayed 34-fold binding selectivity for LXRβ over LXRα (LXRβ IC50 = 16 nM), good activity for inducing ABCA1 gene expression in a THP macrophage cell line, desired weak potency in the LXRα Gal4 functional assay, and low blood–brain barrier penetration in rat. 相似文献
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Ronald C. Bernotas Robert R. Singhaus David H. Kaufman Jeremy M. Travins John W. Ullrich Rayomand Unwalla Elaine Quinet Mark Evans Ponnal Nambi Andrea Olland Björn Kauppi Anna Wilhelmsson Annika Goos-Nilsson Jay Wrobel 《Bioorganic & medicinal chemistry letters》2010,20(1):209-212
A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRβ binding IC50 values <10 nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC50 values <10 nM and were as efficacious as T0901317. 相似文献
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Ying Wang Guihong Li Siyu Yang Xiaoyi Gu Xinyu Li Mingyang Liu Xiujuan Wu Yun Guan Rayomand Press Jie Zhu Hong-Liang Zhang 《PloS one》2015,10(12)