Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors.

abstract：:The tropane derived compounds, 4-[(8-alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-d iethylbenzamides (5a-d), were synthesized and found to have high affinity and selectivity for the delta receptor. Compounds 5a-d are structurally similar to the full agonist (-)-RTI-5989-54 (3); yet, efficacy studies for com...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thomas JB,Atkinson RN,Rothman RB,Burgess JP,Mascarella SW,Dersch CM,Xu H,Carroll FI

更新日期：2000-06-05 00:00:00

abstract：:The biological activity for a set of melanocortin-4 receptor (MC4R) agonists containing a piperazine core with an ortho-substituted aryl sulfonamide is described. Compounds from this set had binding and functional activities at MC4R less than 30 nM. The most selective compound in this series was >25,000-fold more pote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fotsch C,Han N,Arasasingham P,Bo Y,Carmouche M,Chen N,Davis J,Goldberg MH,Hale C,Hsieh FY,Kelly MG,Liu Q,Norman MH,Smith DM,Stec M,Tamayo N,Xi N,Xu S,Bannon AW,Baumgartner JW

更新日期：2005-03-15 00:00:00

abstract：:N(tau)-Aryl-histidine derivatives were synthesized using a modified one-step Cu-catalyzed coupling of aryl halides and N-acetylhistidine methyl ester. The latter is much less reactive than imidazole toward aryl halides. p-Chloroiodobenzene coupled with iodine displacement only, whereas m- and p-bromoiodobenzene both g...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yue W,Lewis SI,Koen YM,Hanzlik RP

更新日期：2004-04-05 00:00:00

abstract：:In order to investigate the relationship between tyrosine phosphorylation of β-catenin and transcriptional activity of β-catenin in Hela and Bcap-37 cells, genistein (a tyrosine kinase inhibitor) was used to inhibit tyrosine phosphorylation in cells. Our results showed the total β-catenin protein levels were mainly eq...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qian HY,Zhang DG,Wang HW,Pei DS,Zheng JN

更新日期：2014-06-01 00:00:00

abstract：:Trifluoromethyl ketones were found to be inhibitors of histone deacetylases (HDACs). Optimization of this series led to the identification of submicromolar inhibitors such as 20 that demonstrated antiproliferative effects against the HT1080 and MDA 435 cell lines. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Frey RR,Wada CK,Garland RB,Curtin ML,Michaelides MR,Li J,Pease LJ,Glaser KB,Marcotte PA,Bouska JJ,Murphy SS,Davidsen SK

更新日期：2002-12-02 00:00:00

abstract：:Bioassay-guided fractionation of the fruit powder of graviola (Annona muricata) yielded three novel compounds: muricins J, K, and L. The compounds are all C35 Annonaceous acetogenins with a mono-tetrahydrofuran ring and four hydroxyls. Their structures were elucidated by spectral methods and chemical modification afte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun S,Liu J,Kadouh H,Sun X,Zhou K

更新日期：2014-06-15 00:00:00

abstract：:A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran scaffolds were designed and synthesized. Optimization of the alkyl substituent in the pyran ring showed preference for an n-propyl group, while 5,8-disubsti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gopalsamy A,Aplasca A,Ciszewski G,Park K,Ellingboe JW,Orlowski M,Feld B,Howe AY

更新日期：2006-01-15 00:00:00

abstract：:West Nile Virus (WNV) is a potentially deadly mosquito-borne flavivirus which has spread rapidly throughout the world. Currently there is no effective vaccine against flaviviral infections. We previously reported the identification of pyrazole ester derivatives as allosteric inhibitors of WNV NS2B-NS3 proteinase. Thes...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sidique S,Shiryaev SA,Ratnikov BI,Herath A,Su Y,Strongin AY,Cosford ND

更新日期：2009-10-01 00:00:00

abstract：:In this report we detail the evolution of our previously reported thiophene isoxazole BET inhibitor chemotype exemplified by CPI-3 to a novel bromodomain selective chemotype (the methyl isoxazoleazepine chemotype) exemplified by carboxamide 23. The methyl isoxazoleazepine chemotype provides potent inhibition of the br...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hewitt MC,Leblanc Y,Gehling VS,Vaswani RG,Côté A,Nasveschuk CG,Taylor AM,Harmange JC,Audia JE,Pardo E,Cummings R,Joshi S,Sandy P,Mertz JA,Sims RJ 3rd,Bergeron L,Bryant BM,Bellon S,Poy F,Jayaram H,Tang Y,Albrecht

更新日期：2015-05-01 00:00:00

abstract：:In order to obtain information regarding the design of selective DPP4 inhibitors, a 3D-QSAR study was conducted using DPP4, DPP8, and DPP9 inhibitors including newly synthesized six- and seven-membered cyclic hydrazine derivatives (KR64300, KR64301), which were evaluated in vitro for their inhibition of DPP4, DPP8, an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang NS,Ahn JH,Kim SS,Chae CH,Yoo SE

更新日期：2007-07-01 00:00:00

abstract：:Mandelate racemase has been studied as a paradigm for enzyme-catalyzed abstraction of a proton from carbon acids with relatively high pKa values. 1,1-Diphenyl-1-hydroxymethylphosphonate is a substrate-intermediate-product analogue and is a modest competitive inhibitor of the enzyme (Ki=1.41+/-0.09 mM), suggesting that...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burley RK,Bearne SL

更新日期：2005-10-01 00:00:00

abstract：:The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles. An X-ray crystal structure of a key anal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar DV,Rai R,Brameld KA,Riggs J,Somoza JR,Rajagopalan R,Janc JW,Xia YM,Ton TL,Hu H,Lehoux I,Ho JD,Young WB,Hart B,Green MJ

更新日期：2012-01-01 00:00:00

abstract：:A single-step sensing system was developed to visually detect ligands of a cleavase-like RNA aptazyme at room temperature using aptazyme-tethered gold nanoparticles, the electrosteric stability of which was adjusted by increasing their diameter. In this system, the ligand induces self-cleavage of the aptazyme on gold ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ogawa A

更新日期：2011-01-01 00:00:00

abstract：:A series of a novel hybrid compounds between nitazoxanide and N-methylbenzimidazole were synthesized starting from the corresponding N-methyl-2-nitroanilines. The new hybrid compounds (1-13) were evaluated in vitro against Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis. NTZ, MTZ and ABZ were used a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Soria-Arteche O,Hernández-Campos A,Yépez-Mulia L,Trejo-Soto PJ,Hernández-Luis F,Gres-Molina J,Maldonado LA,Castillo R

更新日期：2013-12-15 00:00:00

abstract：:Aminoglycosides have been shown to target A-form nucleic acids. Our work has previously shown that neomycin (and other aminoglycosides) bind and stabilize DNA/RNA triplexes and other A-form nucleic acids. We report herein the unexpected B-form duplex stabilization shown by aminoglycoside dimers (neomycin-neomycin and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arya DP,Coffee RL Jr,Xue L

更新日期：2004-09-20 00:00:00

abstract：:α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evalua...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang JJ,Zhang ZH,He F,Liu XW,Xu XJ,Dai LJ,Liu QM,Yuan M

更新日期：2018-02-15 00:00:00

abstract：:The biosynthetic gene cluster of brassicicene C was identified in Alternaria brassicicola strain ATCC 96836 from genome database search. In vivo and in vitro study clearly revealed the function of Orf8 and Orf6 as a fusicoccadiene synthase and methyltransferase, respectively. The understanding toward the biosynthetic ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Minami A,Tajima N,Higuchi Y,Toyomasu T,Sassa T,Kato N,Dairi T

更新日期：2009-02-01 00:00:00

abstract：:Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shiomi S,Wada K,Umeda Y,Kato H,Tsukamoto S,Ishikawa H

更新日期：2018-09-01 00:00:00

abstract：:Here we report a number of novel JS-K structural analogues with sub-micromolar anti-proliferative activities against human leukemia cell lines HL-60 and U937; JS-K is the anti-cancer lead compound O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. The ability of these compounds to g...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nandurdikar RS,Maciag AE,Citro ML,Shami PJ,Keefer LK,Saavedra JE,Chakrapani H

更新日期：2009-05-15 00:00:00

abstract：:A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu M,Mierzwa R,He L,King A,Patel M,Pichardo J,Hart A,Butkiewicz N,Puar MS

更新日期：1999-07-19 00:00:00

abstract：:A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ruel R,L'Heureux A,Thibeault C,Lapointe P,Martel A,Qiao JX,Hua J,Price LA,Wu Q,Chang M,Zheng J,Huang CS,Wexler RR,Rehfuss R,Lam PY

更新日期：2013-12-15 00:00:00

abstract：:A serendipitous discovery that the metalloprotease binding profile of a novel class of 2-carboxamide-3-hydroxamic acid piperidines could be significantly attenuated by the modification of the unexplored P1 substituent enabled the design and synthesis of a novel 2-carboxamide-1-hydroxamic acid cyclohexyl scaffold core ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Burns DM,Li YL,Shi E,He C,Xu M,Zhuo J,Zhang C,Qian DQ,Li Y,Wynn R,Covington MB,Katiyar K,Marando CA,Fridman JS,Scherle P,Friedman S,Metcalf B,Yao W

更新日期：2009-07-01 00:00:00

abstract：:In the search for plants, containing compounds with α-glucosidase inhibitory activity, we found that a methanolic extract from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen significantly inhibited rat intestinal sucrase in vitro. A phytochemical investigation of the aqueous layer of an A. clypearia ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thao NP,Luyen BT,Vinh le B,Lee JY,Kwon YI,Kim YH

更新日期：2016-09-01 00:00:00

abstract：:PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studie...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nankervis JL,Feil SC,Hancock NC,Zheng Z,Ng HL,Morton CJ,Holien JK,Ho PW,Frazzetto MM,Jennings IG,Manallack DT,Martin TJ,Thompson PE,Parker MW

更新日期：2011-12-01 00:00:00

abstract：:We report the synthesis of 3-phenethylazetidine derivatives 2 and their biological activities against 5-HT, NE and DA transporters as well as microsomal stability, CYP inhibition, and hERG inhibition profiles. Compound 2at showed most potent triple reuptake inhibitor with good selectivity as a candidate for depression...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yun J,Han M,Song C,Cheon SH,Choi K,Hahn HG

更新日期：2014-08-01 00:00:00

abstract：:Arenobufagin is a naturally occurring bufadienolide showing promising antitumor activity accompanied however with apparent cardiac toxicity. Following the recent discovery that oxidative damage possibly be an important cause of the cardiac toxicity of cardenolides, a strategy fusing the antitumor agent arenobufagin wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hou W,Huang ZX,Xu HG,Lin J,Zhang DM,Peng QL,Lin H,Chang YQ,Wang LH,Yao Z,Sun PH,Chen WM

更新日期：2018-11-01 00:00:00

abstract：:The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the tw...

journal_title：Bioorganic & medicinal chemistry letters

authors： Menchise V,De Simone G,Di Fiore A,Scozzafava A,Supuran CT

更新日期：2006-12-15 00:00:00

abstract：:A stereocontrolled synthetic route has been used to prepare two of the geometric isomers of all-trans-GGPP. Neither of these isomers is effective substrates for mammalian GGTase I, but 3 is a potent inhibitor of this enzyme (IC(50)=100 nM). Surprisingly, both compounds are effective substrates for mammalian FTase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zahn TJ,Whitney J,Weinbaum C,Gibbs RA

更新日期：2001-06-18 00:00:00

abstract：:Selective inhibition of the aspartyl protease renin has gained attraction as an interesting approach to control hypertension and associated cardiovascular risk factors given its unique position in the renin-angiotensin system. Using a combination of high-throughput screening, parallel synthesis, X-ray crystallography ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Scheiper B,Matter H,Steinhagen H,Stilz U,Böcskei Z,Fleury V,McCort G

更新日期：2010-11-01 00:00:00

abstract：:Structure-activity relationships for a recently discovered thiazolyl phenyl ether series of acetyl-CoA carboxylase (ACC) inhibitors were investigated. Preliminary efforts to optimize the series through modification of the distal aryl ether moiety of the lead scaffold resulted in the identification of compounds exhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Clark RF,Zhang T,Xin Z,Liu G,Wang Y,Hansen TM,Wang X,Wang R,Zhang X,Frevert EU,Camp HS,Beutel BA,Sham HL,Gu YG

更新日期：2006-12-01 00:00:00