共查询到20条相似文献,搜索用时 0 毫秒
1.
Govinda Rao B Bandarage UK Wang T Come JH Perola E Wei Y Tian SK Saunders JO 《Bioorganic & medicinal chemistry letters》2007,17(8):2250-2253
A series of potent thiol-containing aryl sulfonamide TACE inhibitors was designed and synthesized. The SAR and MMP selectivity of the series were investigated. In particular, compound 4b has shown excellent in vitro potency against the isolated TACE enzyme and good selectivity over MMP-2, -7, -8, -9, and -13. The X-ray structure of 4b bound to TACE was obtained. 相似文献
2.
The C46 terminus of phorboxazole A has been modified to incorporate a biotin-terminated linker via direct palladium-mediated Sonogashira reaction conditions. Synthetic 45,46-dehydrobromophorboxazole A was joined with a tris-(polyethyleneglycol)vinyl iodide-biotin ester using catalytic PdCl(2)(PPh(3))(2), CuI, and Et(3)N in THF. This process demonstrates the utility of mild carbon-carbon bond formation in the context of phorboxazoles' architecture and provides a potential affinity probe. 相似文献
3.
Facile synthesis of substituted thiophenes via Pd/C-mediated sonogashira coupling in water 总被引:1,自引:0,他引:1
Raju S Kumar PR Mukkanti K Annamalai P Pal M 《Bioorganic & medicinal chemistry letters》2006,16(24):6185-6189
The first successful Pd/C-mediated Sonogashira coupling of iodothiophene with terminal alkynes in water is described here. Pd/C-CuI-PPh3 was found to be an efficient catalyst system for this coupling reaction. Using this economic and reliable process a variety of acetylenic thiophenes with a wide range of functional groups were prepared in good yields. Synthetic applications and in vitro anticancer properties of some of the compounds synthesized are described. 相似文献
4.
Bandarage UK Wang T Come JH Perola E Wei Y Rao BG 《Bioorganic & medicinal chemistry letters》2008,18(1):44-48
A series of potent thiol-containing aryl sulfone TACE inhibitors were designed and synthesized. The SAR and MMP selectivity of the series were investigated. In particular, compound 8b showed excellent in vitro potency against the isolated enzyme and good selectivity over MMP-2, -7, -8, -9, and -13. The X-ray structure of 8b in complex with TACE was also obtained. 相似文献
5.
In this article, we focus on the synthesis of aryl C-glycosides via Heck coupling. It is organized based on the type of structures used in the assembly of the C-glycosides (also called C-nucleosides) with the following subsections: pyrimidine C-nucleosides, purine C-nucleosides, and monocyclic, bicyclic, and tetracyclic C-nucleosides. The reagents and conditions used for conducting the Heck coupling reactions are discussed. The subsequent conversion of the Heck products to the corresponding target molecules and the application of the target molecules are also described. 相似文献
6.
Levy DE Wang DX Lu Q Chen Z Perumattam J Xu YJ Liclican A Higaki J Dong H Laney M Mavunkel B Dugar S 《Bioorganic & medicinal chemistry letters》2008,18(7):2390-2394
A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the hydrogen bond donating potential of the maleimide ring. Key interactions with the kinase ATP site and hinge region were found to be consistent with homology modeling predictions. 相似文献
7.
8.
Komoriya S Haginoya N Kobayashi S Nagata T Mochizuki A Suzuki M Yoshino T Horino H Nagahara T Suzuki M Isobe Y Furugoori T 《Bioorganic & medicinal chemistry》2005,13(12):3927-3954
Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b. 相似文献
9.
Jagrat M Behera J Yabanoglu S Ercan A Ucar G Sinha BN Sankaran V Basu A Jayaprakash V 《Bioorganic & medicinal chemistry letters》2011,21(14):4296-4300
Twenty-two pyrazoline derivatives were synthesized and tested for their human MAO (hMAO) inhibitory activity. Twelve molecules with unsubstituted ring A and substituted ring C (5-16) were found to be potent inhibitors of hMAO-A isoform with SIMAO-A in the order 103 and 104. Ten molecules with unsubstituted ring A and without ring C (21-30), in which eight molecules (21, 23-26, and 28-30) were selective for hMAO-A, one for hMAO-B (22) and the other one non-selective (27). Presence of ring C increases potency as well as SI towards hMAO-A; however its absence decreases both potency and SI towards hMAO-A and hMAO-B. 相似文献
10.
Yamashita A Norton E Petersen PJ Rasmussen BA Singh G Yang Y Mansour TS Ho DM 《Bioorganic & medicinal chemistry letters》2003,13(19):3345-3350
A series of Muraymycin analogues was synthesized. These analogues showed excellent antimicrobial activity against gram-positive organisms. These analogues also showed excellent inhibitory activity against the target peptidoglycan biosynthesis enzyme MraY, the cell membrane associated transglycosylase responsible for the formation of Lipid II. 相似文献
11.
Amantullah Ansari Sharad Satalkar Varshavekumar Patil Amit S. Shete Simranjeet Kaur Ashu Gupta Siddhartha Singh Mohd. Raja Daniel L. Severance Sebastián Bernales Sarvajit Chakravarty David T. Hung Son M. Pham Francisco J. Herrera Roopa Rai 《Bioorganic & medicinal chemistry letters》2017,27(2):217-222
EZH2 (enhancer of zeste homologue 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that catalyzes the methylation of lysine 27 of histone H3 (H3K27). Dysregulation of EZH2 activity is associated with several human cancers and therefore EZH2 inhibition has emerged as a promising therapeutic target. Several small molecule EZH2 inhibitors with different chemotypes have been reported in the literature, many of which use a bicyclic heteroaryl core. Herein, we report the design and synthesis of EZH2 inhibitors containing an indoline core. Partial saturation of an indole to an indoline provided lead compounds with nanomolar activity against EZH2, while also improving solubility and oxidative metabolic stability. 相似文献
12.
Wei-Yi Li Wei-Wei Ni Ya-Xi Ye Hai-Lian Fang Xing-Ming Pan Jie-Ling He 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):404-413
Abstract A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16?±?0.05 and 3.86?±?0.10?µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (k off=1.60?×?10?3 s?1) from the catalytic domain. 相似文献
13.
Bärbel Wittel Till Vogel Heiko Scharl Sven Nerdinger Bernd Lehnemann Andreas Meudt Victor Snieckus 《Bioorganic & medicinal chemistry》2018,26(15):4583-4593
The use of two biphenyl sulfonic acid ligands for the catalytic C-N cross coupling of aryl halides with anilines, 3-aminopyridine, and secondary amines is reported. Our results represent a significant improvement compared to state of the art methods especially with regards to the removal of palladium. 相似文献
14.
Whittamore PR Addie MS Bennett SN Birch AM Butters M Godfrey L Kenny PW Morley AD Murray PM Oikonomakos NG Otterbein LR Pannifer AD Parker JS Readman K Siedlecki PS Schofield P Stocker A Taylor MJ Townsend LA Whalley DP Whitehouse J 《Bioorganic & medicinal chemistry letters》2006,16(21):5567-5571
Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography. 相似文献
15.
Robert P. Sellers Leslie D. Alexander Victoria A. Johnson Chun-Chieh Lin Jeremiah Savage Ricardo Corral Jason Moss Tim S. Slugocki Erinprit K. Singh Melinda R. Davis Suchitra Ravula Jamie E. Spicer Jenna L. Oelrich Andrea Thornquist Chung-Mao Pan Shelli R. McAlpine 《Bioorganic & medicinal chemistry》2010,18(18):6822-6856
Utilizing the structure–activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90’s binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative. 相似文献
16.
Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure,synthesis, and SAR
Tetsuo Takayama Hiroki Umemiya Hideaki Amada Tetsuya Yabuuchi Fumiyasu Shiozawa Hironori Katakai Akiko Takaoka Akie Yamaguchi Mayumi Endo Masakazu Sato 《Bioorganic & medicinal chemistry letters》2010,20(1):108-111
We have described the synthesis, enzyme inhibitory activity, structure–activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC50s <10 nM) for Lck kinase inhibition. 相似文献
17.
Provins L Christophe B Danhaive P Dulieu J Durieu V Gillard M Lebon F Lengelé S Quéré L van Keulen B 《Bioorganic & medicinal chemistry letters》2006,16(7):1834-1839
SAR around 4,6-diaminopyrimidine derivatives allowed the discovery of the first potent dual M(3) antagonists and PDE4 inhibitors. Various chemical modulations around that scaffold led to the discovery of ucb-101333-3 which is characterized by the most interesting profile on both targets. 相似文献
18.
Zhao L Zhang Y Dai C Guzi T Wiswell D Seghezzi W Parry D Fischmann T Siddiqui MA 《Bioorganic & medicinal chemistry letters》2010,20(24):7216-7221
A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM. 相似文献
19.
Grant EB Guiadeen D Baum EZ Foleno BD Jin H Montenegro DA Nelson EA Bush K Hlasta DJ 《Bioorganic & medicinal chemistry letters》2000,10(19):2179-2182
Beta-lactam antibiotics such as the cephalosporins and penicillins have diminished clinical effectiveness due to the hydrolytic activity of diverse beta-lactamases, especially those in molecular classes A and C. A structure activity relationship (SAR) study of a high-throughput screening lead resulted in the discovery of a potent and selective non-beta-lactam inhibitor of class C beta-lactamases. 相似文献
20.
Sutton JC Bolton SA Davis ME Hartl KS Jacobson B Mathur A Ogletree ML Slusarchyk WA Zahler R Seiler SM Bisacchi GS 《Bioorganic & medicinal chemistry letters》2004,14(9):2233-2239
A series of nonguanidine N1-activated C4-carboxy azetidinone tryptase inhibitors was prepared by solid-phase methodology to quickly assess the SAR associated with distal functionality on the N1-activating group. From these studies, potent inhibitors with improved specificity were discovered. 相似文献