排序方式: 共有41条查询结果,搜索用时 31 毫秒
1.
Estaras Matias Ortiz-Placin Candido Castillejo-Rufo Alba Fernandez-Bermejo Miguel Blanco Gerardo Mateos Jose M. Vara Daniel Gonzalez-Cordero Pedro L. Chamizo Sandra Lopez Diego Rojas Adela Jaen Isabel de Armas Noelia Salido Gines M. Iovanna Juan L. Santofimia-Castaño Patricia Gonzalez Antonio 《Journal of physiology and biochemistry》2023,79(1):235-249
Journal of Physiology and Biochemistry - We have investigated the effects of melatonin on major pathways related with cellular proliferation and energetic metabolism in pancreatic stellate cells.... 相似文献
2.
Schwarz RD Spencer CJ Jaen JC Mirzadegan T Moreland D Tecle H Thomas AJ 《Life sciences》1995,56(11-12):923-929
Aspartate 103 (D103) in the third transmembrane domain of the Hm2 receptor was mutated to glutamate (D103E), asparagine (D103N), or alanine (D103A). As measured by [3H]-NMS, no significant binding was observed in D103A, while a 2-fold decrease in ligand affinity was seen in D103E and a 32-fold decrease in affinity was found in the D103N mutant. Examination of reference agonists showed greater loss of affinity in D103N than in D103E with the rank order of change being: L-607,207>carbachol>arecoline>pilocarpine>oxotremorine>McN-A-343. Of the novel 1-azabicyclo[2.2.1]-heptan-3-one oxime agonists examined, arylacetylene oximes showed little alteration in binding in either the D103E or D103N mutants, while the geometric isomers of several bicyclic aryl-ene-yne oximes showed significant changes in affinity, especially in the D103N mutant. Thus, overall size of the agonist and/or spatial orientation of the molecule within the binding pocket contribute to changes measured in binding. 相似文献
3.
Cushing TD Baichwal V Berry K Billedeau R Bordunov V Broka C Browner MF Cardozo M Cheng P Clark D Dalrymple S DeGraffenreid M Gill A Hao X Hawley RC He X Labadie SS Labelle M Lehel C Lu PP McIntosh J Miao S Parast C Shin Y Sjogren EB Smith ML Talamas FX Tonn G Walker KM Walker NP Wesche H Whitehead C Wright M Jaen JC 《Bioorganic & medicinal chemistry letters》2011,21(1):423-426
A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model. 相似文献
4.
Chen X Mihalic J Fan P Liang L Lindstrom M Wong S Ye Q Fu Y Jaen J Chen JL Dai K Li L 《Bioorganic & medicinal chemistry letters》2012,22(1):363-366
A series of spiropiperidine carbazoles were synthesized and evaluated as MCHR2 antagonists using a FLIPR assay. The pharmacokinetic properties of selected compounds have also been studied. This effort led to the discovery of potent and specific MCHR2 antagonists. Compound 38 demonstrated good pharmacokinetic properties across rat, beagle dog and rhesus monkey and had a favorable selectivity profile against a number of other receptors. These MCHR2 antagonists are considered appropriate tool compounds for study of the function of MCHR2 in vivo. 相似文献
5.
Mihalic JT Fan P Chen X Chen X Fu Y Motani A Liang L Lindstrom M Tang L Chen JL Jaen J Dai K Li L 《Bioorganic & medicinal chemistry letters》2012,22(11):3781-3785
An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the potent MCHR1 antagonist 11 with a dramatically reduced hERG liability. The decrease in hERG activity was confirmed by several in vivo preclinical cardiovascular studies examining QT prolongation. This compound demonstrated good selectivity for MCHR1 and possessed good pharmacokinetic properties across preclinical species. Compound 11 was also efficacious in reducing body weight in two in vivo mouse models. This compound was selected for clinical evaluation and was given the code AMG 076. 相似文献
6.
X Jiao DJ Kopecky B Fisher DE Piper M Labelle S McKendry M Harrison S Jones J Jaen AK Shiau P Escaron J Danao A Chai P Coward F Kayser 《Bioorganic & medicinal chemistry letters》2012,22(18):5966-5970
The present report describes our efforts to convert an existing LXR agonist into an LXR antagonist using a structure-based approach. A series of benzenesulfonamides was synthesized based on structural modification of a known LXR agonist and was determined to be potent dual liver X receptor (LXR α/β) ligands. Herein we report the identification of compound 54 as the first reported LXR antagonist that is suitable for pharmacological in vivo evaluation in rodents. 相似文献
7.
X Jiao DJ Kopecky J Liu J Liu JC Jaen MG Cardozo R Sharma N Walker H Wesche S Li E Farrelly SH Xiao Z Wang F Kayser 《Bioorganic & medicinal chemistry letters》2012,22(19):6212-6217
Two classes of ACK1 inhibitors, 4,5,6-trisubstituted furo[2,3-d]pyrimidin4-amines and 4,5,6-trisubstituted 7H-pyrrolo[2,3-d]pyrimidin-4-amines, were discovered and evaluated as ACK1 inhibitors. Further structural refinement led to the identification of potent and selective dithiolane inhibitor 37. 相似文献
8.
Yosup Rew Dustin L. McMinn Zhulun Wang Xiao He Randall W. Hungate Juan C. Jaen Athena Sudom Daqing Sun Hua Tu Stefania Ursu Elisia Villemure Nigel P.C. Walker Xuelei Yan Qiuping Ye Jay P. Powers 《Bioorganic & medicinal chemistry letters》2009,19(6):1797-1801
Discovery and optimization of a piperidyl benzamide series of 11β-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives. 相似文献
9.
Cushing TD Adrian J Chen X DiMaio H Doughan B Flygare J Liang L Mayorga V Miao S Mellon H Peterson MG Powers JP Spector F Stein C Wright M Xu D Ye Q Jaen J 《Bioorganic & medicinal chemistry letters》2006,16(18):4879-4883
Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles. 相似文献
10.
Waka Yokoyama Hitoshi Kohsaka Kayoko Kaneko Matthew Walters Aiko Takayasu Shin Fukuda Chie Miyabe Yoshishige Miyabe Paul E Love Nobuhiro Nakamoto Takanori Kanai Kaori Watanabe-Imai Trevor T Charvat Mark ET Penfold Juan Jaen Thomas J Schall Masayoshi Harigai Nobuyuki Miyasaka Toshihiro Nanki 《Arthritis research & therapy》2014,16(5)