- Identification and initial SAR of silybin: An Hsp90 inhibitor
[作者：Zhao, HP; Brandt, GE; Galam, L; Matts, RL; Blagg, BSJ,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2659-2664 , 文章类型： Article，,卷期：2011年21-9]
- Through Hsp90-dependent firefly luciferase refolding and Hsp90-dependent heme-regulated eIF2 alpha kinase (HRI) activation assays, silybin was identified as a novel Hsp90 inhibitor. Subsequently, a library of silybin ana...
- Design of potent and selective GPR119 agonists for type II diabetes
[作者：Szewczyk, JW; Acton, J; Adams, AD; Chicchi, G; Freeman, S; Howard, AD; Huang, Y; Li, C; Meinke, PT; Mosely, R; Murphy, E; Samuel, R; Santini, C; Yang, M; Zhang, Y; Zhao, KK; Wood, HB,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2665-2669 , 文章类型： Article，,卷期：2011年21-9]
- Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC(50) = 3600 nM). Dual termini optimization of 1 led to compound 36 having improved potency, selectivity, and formulatio...
- Enediol mimics as inhibitors of the D-arabinose 5-phosphate isomerase (KdsD) from Francisella tularensis
[作者：Yep, A; Sorenson, RJ; Wilson, MR; Showalter, HDH; Larsen, SD; Keller, PR; Woodard, RW,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2679-2682 , 文章类型： Article，,卷期：2011年21-9]
- We explored the D-arabinose 5-phosphate isomerase (KdsD, E.C. 5.3.1.13) from Francisella tularensis, a highly infectious Gram-negative pathogen that has raised concern as a potential bioweapon, as a target for the develo...
- Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: Discovery of MK-2918
[作者：Paone, DV; Nguyen, DN; Shaw, AW; Burgey, CS; Potteiger, CM; Deng, JZ; Mosser, SD; Salvatore, CA; Yu, S; Roller, S; Kane, SA; Selnick, HG; Vacca, JP; Williams, TM,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2683-2686 , 文章类型： Article，,卷期：2011年21-9]
- In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identifi...
- Acylideneoxoindoles: A new class of reversible inhibitors of human transglutaminase 2
[作者：Klock, C; Jin, X; Choi, KH; Khosla, C; Madrid, PB; Spencer, A; Raimundo, BC; Boardman, P; Lanza, G; Griffin, JH,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2692-2696 , 文章类型： Article，,卷期：2011年21-9]
- Inhibitors of human transglutaminase 2 (TG2) are anticipated to be useful in the therapy of a variety of diseases including celiac sprue as well as certain CNS disorders and cancers. A class of 3-acylidene-2-oxoindoles w...
- Discovery and optimization of a novel, selective and brain penetrant M-1 positive allosteric modulator (PAM): The development of ML169, an MLPCN probe
[作者：Reid, PR; Bridges, TM; Sheffler, DJ; Cho, HP; Lewis, LM; Days, E; Daniels, JS; Jones, CK; Niswender, CM; Weaver, CD; Conn, PJ; Lindsley, CW; Wood, MR,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2697-2701 , 文章类型： Article，,卷期：2011年21-9]
- This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M-1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach...
- Synthesis of 'clickable' acylhomoserine lactone quorum sensing probes: Unanticipated effects on mammalian cell activation
[作者：Garner, AL; Yu, J; Struss, AK; Lowery, CA; Zhu, J; Kim, SK; Park, J; Mayorov, AV; Kaufmann, GF; Kravchenko, VV; Janda, KD,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2702-2705 , 文章类型： Article，,卷期：2011年21-9]
- Alkynyl- and azido-tagged 3-oxo-C-12-acylhomoserine lactone probes have been synthesized to examine their potential utility as probes for discovering the mammalian protein target of the Pseudomonas aeruginosa autoinducer...
- Experimental and theoretical investigation of the scope of enantioselective ketone allylations employing Nakamura's allylzinc-bisoxazoline reagent
[作者：Johnson, AG; Loertscher, BM; Moeck, AR; Matthews, SS; Ess, DH; Castle, SL,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2706-2710 , 文章类型： Article，,卷期：2011年21-9]
- The scope of enantioselective allylations employing Nakamura's allylzinc-bisoxazoline reagent was examined by performing allylations of a selection of readily available ketones. Low-to-moderate ee's were observed, and a ...
- Discovery of molecular switches within the ADX-47273 mGlu(5) PAM scaffold that modulate modes of pharmacology to afford potent mGlu(5) NAMs, PAMs and partial antagonists
[作者：Lamb, JP; Engers, DW; Niswender, CM; Rodriguez, AL; Venable, DF; Conn, PJ; Lindsley, CW,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2711-2714 , 文章类型： Article，,卷期：2011年21-9]
- This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtl...
- Pyrimido[4,5-d]azepines as potent and selective 5-HT2C receptor agonists: Design, synthesis, and evaluation of PF-3246799 as a treatment for urinary incontinence
[作者：Andrews, MD; Fish, PV; Blagg, J; Brabham, TK; Brennan, PE; Bridgeland, A; Brown, AD; Bungay, PJ; Conlon, KM; Edmunds, NJ; af Forselles, K; Gibbons, CP; Green, MP; Hanton, G; Holbrook, M; Jessiman, AS; McIntosh, K; McMurray, G; Nichols, CL; Root, JA; Storer, RI; Sutton, MR; Ward, RV; Westbrook, D; Whitlock, GA,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2715-2720 , 文章类型： Article，,卷期：2011年21-9]
- New pyrimido[4,5-d]azepines 7 are disclosed as potent 5-HT2C receptor agonists. A preferred example, 7b had minimal activation at either the 5-HT2A or 5-HT2B receptors combined with robust efficacy in a preclinical canin...
- The discovery of high affinity agonists of GPR109a with reduced serum shift and improved ADME properties
[作者：Imbriglio, JE; DiRocco, D; Bodner, R; Raghavan, S; Chen, WC; Marley, D; Esser, C; Holt, TG; Wolff, MS; Taggart, AKP; Waters, MG; Tata, JR; Colletti, SL,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2721-2724 , 文章类型： Article，,卷期：2011年21-9]
- Amino-anthranilic acid derivatives have been identified as a new class of low serum shifted, high affinity full agonists of the human orphan G-protein-coupled receptor GPR109a with improved ADME properties. (C) 2010 Else...
- Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: A bench-to-bedside case study on tissue selective drug distribution
[作者：Pfefferkorn, JA; Litchfield, J; Hutchings, R; Cheng, XM; Larsen, SD; Auerbach, B; Bush, MR; Lee, C; Erasga, N; Bowles, DM; Boyles, DC; Lu, GN; Sekerke, C; Askew, V; Hanselman, JC; Dillon, L; Lin, ZW; Robertson, A; Olsen, K; Boustany, C; Atkinson, K; Goosen, TC; Sahasrabudhe, V; Chupka, J; Duignan, DB; Feng, B; Scialis, R; Kimoto, E; Bi, YA; Lai, YR; El-Kattan, A; Bakker-Arkema, R; Barclay, P; Kindt, E; Le, V; Mandema, JW; Milad, M; Tait, BD; Kennedy, R; Trivedi, BK; Kowala, M,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2725-2731 , 文章类型： Article，,卷期：2011年21-9]
- The design of drugs with selective tissue distribution can be an effective strategy for enhancing efficacy and safety, but understanding the translation of preclinical tissue distribution data to the clinic remains an im...
- Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors
[作者：Noel, R; Shin, Y; Song, XY; He, YJ; Koenig, M; Chen, WM; Ling, YY; Lin, L; Ruiz, CH; LoGrasso, P; Cameron, MD; Duckett, DR; Kamenecka, TM,期刊：Bioorganic & Medicinal Chemistry Letters, 页码：2732-2735 , 文章类型： Article，,卷期：2011年21-9]
- The design and synthesis of a novel series of c-jun N-terminal kinase (JNK) inhibitors is described. The development of the 4-(pyrazol-3-yl)-pyridine series was discovered from an earlier pyrimidine series of JNK inhibit...
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