Recent encounters with atropisomerism in drug discovery.

abstract：:Triptolide (TP) is a diterpene epoxide component extracted from Tripterygium wilfordii and has been shown to possess an impressive anticancer effect. However, TP has not yet entered any clinic trials due to the severe adverse effects that resulted from the off-target absorption and distribution found in animal studies...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lou D,Lou Z,Lin Y,Shangguan H,Lin Y,Luo Q,Zhang H,Lin G,Chen R,Kou L,Bao S

更新日期：2020-12-17 00:00:00

abstract：:Novel derivatives of the highly potent and selective histamine H3-receptor antagonist ciproxifan (3) with different chain lengths as well as with structural variants of the cyclopropyl ketone moiety have been prepared and screened for their antagonist H3-receptor potencies in vitro and in vivo. Some derivatives (2, 6-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stark H,Ligneau X,Sadek B,Ganellin CR,Arrang JM,Schwartz JC,Schunack W

更新日期：2000-10-16 00:00:00

abstract：:Fragment-based NMR screening of a small literature focused library led to identification of a historical thrombin/FactorXa building block, 17A, that was found to be a ROCK-I inhibitor. In the absence of an X-ray structure, fragment growth afforded 6-substituted isoquinolin-1-amine derivatives which were profiled in th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ray P,Wright J,Adam J,Bennett J,Boucharens S,Black D,Cook A,Brown AR,Epemolu O,Fletcher D,Haunso A,Huggett M,Jones P,Laats S,Lyons A,Mestres J,de Man J,Morphy R,Rankovic Z,Sherborne B,Sherry L,van Straten N,We

更新日期：2011-01-01 00:00:00

abstract：:A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Boot JR,Boulet SL,Clark BP,Cases-Thomas MJ,Delhaye L,Diker K,Fairhurst J,Findlay J,Gallagher PT,Gilmore J,Harris JR,Masters JJ,Mitchell SN,Naik M,Simmonds RG,Smith SM,Richards SJ,Timms GH,Whatton MA,Wolfe CN,Wood

更新日期：2006-05-15 00:00:00

abstract：:The first enantioselective biocatalytic synthesis of (S)-monastrol has been developed via an unexpected and unusual enzymatic pathway as suitable route. Whereas attempts for a direct hydrolysis of racemic monastrol were not successful, formation of racemic O-butanoyl monastrol and subsequent enantioselective hydrolysi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blasco MA,Thumann S,Wittmann J,Giannis A,Gröger H

更新日期：2010-08-01 00:00:00

abstract：:A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 were synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6-ethynylpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the activated 1,2,4-triazole intermediate 6. Compound 7 was used as the key intermediate for the pre...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gossett LS,Habeck LL,Shackelford KA,Mendelsohn LG,Gates SB,Worzalla JF,Self TD,Theobald KS,Andis SL,Schultz RM,Shih C

更新日期：1999-01-04 00:00:00

abstract：:Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Robinson RP,Bartlett JA,Bertinato P,Bessire AJ,Cosgrove J,Foley PM,Manion TB,Minich ML,Ramos B,Reese MR,Schmahai TJ,Swick AG,Tess DA,Vaz A,Wolford A

更新日期：2011-07-15 00:00:00

abstract：:The synthesis and antibacterial activity of 2,5-dihydropyrrole formyl hydroxyamino derivatives are reported. The antibacterial activities of these derivatives were evaluated, and some of these derivatives showed better in vitro antibacterial activity than existing drugs, including penicillin, ciprofloxacin, vancomycin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi W,Duan Y,Qian Y,Li M,Yang L,Hu W

更新日期：2010-06-15 00:00:00

abstract：:Resveratrol (Rsv) is widely reported to possess anticarcinogenic properties in a plethora of cellular and animal models having limited toxicity toward normal cells. In the molecular level, Rsv can act as a suppressive agent for several impaired signaling pathways on cancer cells. However, Fukuhara and Miyata have show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andrade Volkart P,Benedetti Gassen R,Mühlen Nogueira B,Nery Porto B,Eduardo Vargas J,Arigony Souto A

更新日期：2017-08-01 00:00:00

abstract：:A series of novel 9-O-arylalkyloxime analogs based on three different 16-membered macrolide scaffolds-5-O-mycaminosyltylonolide (OMT), tilmicosin, and 20-deoxy-20-(3,5-dimethyl-1-piperidin-1-yl)-OMT-was synthesized. In vitro antibiotic activities were assayed against Gram-positive Streptococcus pneumoniae and Staphylo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fu H,Marquez S,Gu X,Katz L,Myles DC

更新日期：2006-03-01 00:00:00

abstract：:A versatile and high yielding synthesis of novel androgen receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Altimari JM,Niranjan B,Risbridger GP,Schweiker SS,Lohning AE,Henderson LC

更新日期：2014-11-01 00:00:00

abstract：:Four new peptidyl aldehydes bearing proline mimetics at the P(2)-position were synthesized and studied as inhibitors of calpain I, cathepsin B, and selected serine proteases. The ring size of the P(2)-constraining residue influenced the inhibitory potency and selectivity of the compounds for calpain I compared to the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donkor IO,Korukonda R,Huang TL,LeCour L Jr

更新日期：2003-03-10 00:00:00

abstract：:Alkyl parabens are used as antimicrobial preservatives in cosmetics, food, and pharmaceutical products. However, the mode of action of these chemicals has not been assessed thoroughly. In this study, we determined the effects of alkyl parabens on plant pathogenic fungi. All the fungi tested, were susceptible to parabe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ito S,Yazawa S,Nakagawa Y,Sasaki Y,Yajima S

更新日期：2015-04-15 00:00:00

abstract：:We sought to design dual pharmacology bronchodilators targeting both the M(3) muscarinic acetylcholine and beta-2 adrenergic (β(2)) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hughes AD,Chin KH,Dunham SL,Jasper JR,King KE,Lee TW,Mammen M,Martin J,Steinfeld T

更新日期：2011-03-01 00:00:00

abstract：:A series of 2-phenylspiroindenediones was prepared. The spiroindenediones were found to be less active than the corresponding spiroindenes as estrogen receptor ligands and failed to demonstrate the receptor subtype selectivity that had been anticipated from molecular modeling. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Blizzard TA,Mosley RT,Birzin ET,Chan W,Hammond ML

更新日期：2004-03-08 00:00:00

abstract：:Paclitaxel (PTX) was complexed with beta-cyclodextrin (1), 2,6-dimethyl-beta-cyclodextrin (2) and 2,3,6-trimethyl-beta-cyclodextrin (3). PTX-CYD complexes were characterized both at the solid and liquid states. Experimental findings are in agreement with molecular modeling analysis, which showed different PTX-CYD inte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alcaro S,Ventura CA,Paolino D,Battaglia D,Ortuso F,Cattel L,Puglisi G,Fresta M

更新日期：2002-06-17 00:00:00

abstract：:Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer's disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hroch L,Benek O,Guest P,Aitken L,Soukup O,Janockova J,Musil K,Dohnal V,Dolezal R,Kuca K,Smith TK,Gunn-Moore F,Musilek K

更新日期：2016-08-01 00:00:00

abstract：:A MeOH extract of the dry root of Lithospermum erythrorhizon showed strong increasing effect on serine palmitoyltransferase (SPT) in normal human keratinocyte cells (HaCaT cells). Bioassay-guided separation on this extract using repeated chromatography resulted in the isolation of lithospermic acid (1) and two derivat...

journal_title：Bioorganic & medicinal chemistry letters

authors： Thuong PT,Kang KW,Kim JK,Seo DB,Lee SJ,Kim SH,Oh WK

更新日期：2009-03-15 00:00:00

abstract：:Catalytic disulfenylation reaction of alkenes by common Lewis acids has been investigated in detail. While reactions by FeCl(3) were feasible with cycloalkenes and other simple alkenes, much faster and excellent conversions were possible by AlCl(3) even with the substrates less reactive toward FeCl(3). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamagiwa N,Suto Y,Torisawa Y

更新日期：2007-11-15 00:00:00

abstract：:Sets of isomeric thiazole derivatives 1 and 2 have been synthesised in a parallel iterative solution-phase synthesis approach guided by the SAR analysis derived from biological results and computer-aided design and analysis. This synergistic and streamlined working procedure led to highly active isomeric NPY5 receptor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nettekoven M,Guba W,Neidhart W,Mattei P,Pflieger P,Roche O,Taylor S

更新日期：2005-07-15 00:00:00

abstract：:A novel method to generate RNA binding D-peptide has been developed. To achieve the screening method, phage display was applied to "Mirrored" RNA (L-enantiomer of RNA). We have selected pre-miR21 as an initial screening target to demonstrate the method. The mirrored pre-miR-21 binding peptide sequences were successful...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sakamoto K,Otake K,Umemoto T

更新日期：2017-02-15 00:00:00

abstract：:Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Miyata Y,Fujii H,Uenohara Y,Kobayashi S,Takeuchi T,Nagase H

更新日期：2012-08-15 00:00:00

abstract：:Novel polyhalo 2,4-diaminoquinazolines 3a-3d were prepared by reacting polyhaloisophthalonitriles with guanidine carbonate under solvent-free conditions and in the absence of a catalyst with good yields (74-95%). A series of highly functionalized 2,4-diaminoquinazolines 4-5 were then synthesized based on 3a-3c. The an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan SJ,Zheng H,Huang C,Yan YY,Lin J

更新日期：2010-08-01 00:00:00

abstract：:A new abietane, namely, 20-hydroxyferruginol (1), together with known ferruginol (2), 18-hydroxyferruginol (3), sugiol (4), and 6alpha-hydroxysugiol (5), were isolated from the cones of Sequoia sempervirens. Their structures were elucidated through spectral data. Compounds 1 and 5 strongly inhibited colon, lung, and b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Son KH,Oh HM,Choi SK,Han DC,Kwon BM

更新日期：2005-04-15 00:00:00

abstract：:Two new antiinflammatory macrolides, lobophorins A and B (1 and 2), have been isolated from fermentation broths of a marine bacterium isolated from the surface the Caribbean brown alga Lobophora variegata (Dictyotales). The new compounds, distantly related to antibiotics of the kijanimicin class, are potent inhibitors...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jiang ZD,Jensen PR,Fenical W

更新日期：1999-07-19 00:00:00

abstract：:The design and synthesis of new 1alpha,25-dihydroxy-19-norvitamin D(3) analogues 3a-c, which have an amide bond in the molecule instead of the diene, are described. The A-ring moiety was constructed by a (3S,5S)-3,5-dihydroxypiperidine derivative (9, 11, or 13) prepared from D-mannose, and a CD-ring carboxylic acid 16...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suhara Y,Kittaka A,Ono K,Kurihara M,Fujishima T,Yoshida A,Takayama H

更新日期：2002-12-16 00:00:00

abstract：:Non peptide products have been found to show nanomolar binding and functional affinities at the human tachykinin NK-2 receptor. The new antagonists do not possess stereogenic centers and their thermal behaviour in solution is featured by a peculiar set of conformational stereoisomers. A macroscopic viewpoint is prefer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Altamura M,Canfarini F,Catalioto RM,Guidi A,Pasqui F,Renzetti AR,Triolo A,Maggi CA

更新日期：2002-10-21 00:00:00

abstract：:Synthesis and characterization of an inert perchlorotriphenylmethyl triester radical, PTM-TE, are reported. PTM-TE was prepared by a facile 3-step synthesis using Friedel-Crafts reaction of tetrachlorobenzene with chloroform followed by ethoxycarbonylation and subsequent oxidation. PTM-TE is paramagnetic and exhibits ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dang V,Wang J,Feng S,Buron C,Villamena FA,Wang PG,Kuppusamy P

更新日期：2007-07-15 00:00:00

abstract：:The synthesis of two C-1 analogues of pancratistatin has been accomplished in 17 steps from bromobenzene. The key steps involved the enzymatic dihydroxylation, regioselective opening of epoxyaziridine 9 with the alane derived from 8, a solid-state silica-gel-catalyzed intramolecular opening of aziridine to produce phe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Scattolon J,Hudlicky T,Romero AE,Kornienko A

更新日期：2011-08-15 00:00:00

abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebouvier N,Pagniez F,Duflos M,Le Pape P,Na YM,Le Baut G,Le Borgne M

更新日期：2007-07-01 00:00:00