abstract：:Structural modifications to the coumarin core and benzamide side chain of novobiocin have successfully transformed the natural product from a selective DNA gyrase inhibitor into a potent inhibitor of the Hsp90 C-terminus. However, no SAR studies have been conducted on the noviose appendage, which represents the rate-l...

journal_title：ACS medicinal chemistry letters

authors： Zhao H,Kusuma BR,Blagg BS

更新日期：2010-07-13 00:00:00

abstract：:The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized versio...

journal_title：ACS medicinal chemistry letters

authors： Matsuno K,Masuda Y,Uehara Y,Sato H,Muroya A,Takahashi O,Yokotagawa T,Furuya T,Okawara T,Otsuka M,Ogo N,Ashizawa T,Oshita C,Tai S,Ishii H,Akiyama Y,Asai A

更新日期：2010-07-13 00:00:00

abstract：:GPR40, one of the G protein-coupled receptors predominantly expressed in pancreatic β-cells, mediates enhancement of glucose-stimulated insulin secretion by free fatty acids. A potent and selective GPR40 agonist is theorized to be a safe and effective antidiabetic drug with little or no risk of hypoglycemia. Cyclizati...

journal_title：ACS medicinal chemistry letters

authors： Negoro N,Sasaki S,Mikami S,Ito M,Suzuki M,Tsujihata Y,Ito R,Harada A,Takeuchi K,Suzuki N,Miyazaki J,Santou T,Odani T,Kanzaki N,Funami M,Tanaka T,Kogame A,Matsunaga S,Yasuma T,Momose Y

更新日期：2010-06-18 00:00:00

abstract：:We have developed a novel albumin-binding prodrug of doxorubicin that incorporates p-aminobenzyloxycarbonyl (PABC) as a 1,6 self-immolative spacer in addition to the heptapeptide, Arg-Ser-Ser-Tyr-Tyr-Ser-Leu, as a substrate for the prostate-specific antigen (PSA) that is overexpressed in prostate carcinoma and represe...

journal_title：ACS medicinal chemistry letters

authors： Elsadek B,Graeser R,Warnecke A,Unger C,Saleem T,El-Melegy N,Madkor H,Kratz F

更新日期：2010-05-26 00:00:00

abstract：:We report the discovery of benzoxaborole antitrypanosomal agents and their structure-activity relationships on central linkage groups and different substitution patterns in the sulfur-linked series. The compounds showed in vitro growth inhibition IC50 values as low as 0.02 μg/mL and in vivo efficacy in acute murine in...

journal_title：ACS medicinal chemistry letters

authors： Ding D,Zhao Y,Meng Q,Xie D,Nare B,Chen D,Bacchi CJ,Yarlett N,Zhang YK,Hernandez V,Xia Y,Freund Y,Abdulla M,Ang KH,Ratnam J,McKerrow JH,Jacobs RT,Zhou H,Plattner JJ

更新日期：2010-04-06 00:00:00

abstract：:A novel modulator of sodium ion currents was synthesized in 6 steps from a protected dihydroxypyrrolidine nitrone, via 1,3-dipolar cycloaddition reaction with acrylamide. Sodium ion currents in B50 cells were evaluated in comparison to saxitoxin and tetrodotoxin, and revealed an IC(50) of 15.7 muM. The new compound sh...

journal_title：ACS medicinal chemistry letters

authors： Mao H,Fieber LA,Gawley RE

更新日期：2010-03-31 00:00:00

abstract：:SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism dire...

journal_title：ACS medicinal chemistry letters

authors： Rydberg P,Gloriam DE,Zaretzki J,Breneman C,Olsen L

更新日期：2010-03-15 00:00:00

abstract：:A novel series of quinazolinone T-type calcium channel antagonists have been prepared and evaluated using in vitro and in vivo assays. Optimization of the screening hit 3 by modifications of the 3- and 4-positions of the quinazolinone ring afforded potent and selective antagonists that displayed in vivo central nervou...

journal_title：ACS medicinal chemistry letters

authors： Barrow JC,Rittle KE,Reger TS,Yang ZQ,Bondiskey P,McGaughey GB,Bock MG,Hartman GD,Tang C,Ballard J,Kuo Y,Prueksaritanont T,Nuss CE,Doran SM,Fox SV,Garson SL,Kraus RL,Li Y,Marino MJ,Kuzmick Graufelds V,Uebele VN,R

更新日期：2010-02-01 00:00:00

abstract：:Incorporation of polar functionality into a series of highly potent calcitonin gene-related peptide (CGRP) receptor antagonists was explored in an effort to improve pharmacokinetics. This strategy identified piperazinone analogues that possessed improved solubility at acidic pH and increased oral bioavailability in mo...

journal_title：ACS medicinal chemistry letters

authors： Bell IM,Gallicchio SN,Wood MR,Quigley AG,Stump CA,Zartman CB,Fay JF,Li CC,Lynch JJ,Moore EL,Mosser SD,Prueksaritanont T,Regan CP,Roller S,Salvatore CA,Kane SA,Vacca JP,Selnick HG

更新日期：2010-01-12 00:00:00