Lead optimization of COX-2 inhibitor nimesulide analogs to overcome aromatase inhibitor resistance in breast cancer cells.

abstract：:Optimisation of a series of 4-piperidinyltriazoles led to the identification of compound 28a which showed good whole cell antiviral activity, excellent selectivity over the hERG ion channel and complete oral absorption. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Blakemore DC,Chiva JY,Eastwood RL,Middleton DS,Paradowski KA

更新日期：2009-03-01 00:00:00

abstract：:Several benzofuran derivatives linked to a 3-indoletetrahydropyridine through an alkyl chain were prepared and evaluated for serotonin transporter and 5-HT(1A) receptor affinities. Their design, synthesis and structure-activity relationships are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Venkatesan AM,Dos Santos O,Ellingboe J,Evrard DA,Harrison BL,Smith DL,Scerni R,Hornby GA,Schechter LE,Andree TH

更新日期：2010-02-01 00:00:00

abstract：:A series of newer 1,2,4-triazole-3-thiol derivatives 5(a-m) and 6(a-i) containing a triazole fused with pyrazine moiety of pharmacological significance have been synthesized. All the synthesized compounds were screened for their in vitro antileishmanial and antioxidant activities. Compounds 5f (IC50=79.0µM) and 6f (IC...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patil SR,Asrondkar A,Patil V,Sangshetti JN,Kalam Khan FA,Damale MG,Patil RH,Bobade AS,Shinde DB

更新日期：2017-08-15 00:00:00

abstract：:Thermal transformation of the (+)-catechin (1) with heating processing afforded a new oxidation product, gambiriin D (2), along with catechin [6'-8]-catechin (3), and (+)-epicatechin (4). The structure of a new catechin dimer with C-C linkage was determined on the basis of spectroscopic data interpretation. The catech...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim T,Choi HJ,Eom SH,Lee J,Kim TH

更新日期：2014-03-15 00:00:00

abstract：:Difluorosialic acids (DFSAs) are potent inhibitors of viral neuraminidase that demonstrate activity against oseltamivir- and zanamivir-resistant strains of influenza. Unfortunately, low oral bioavailability precludes their development as second generation neuraminidase inhibitors for treating influenza as this leaves ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Arns S,Tan J,Sun S,Galey A,Zisman N,Ross F,Udechukwu J,Dercho S,Gusti V,Paquette J,Webb M,Bourque E,Withers SG,Liggins R

更新日期：2015-06-15 00:00:00

abstract：:A novel series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). SAR around this series revealed dramatic differences in binding and function in mutant variants (MT) of the AR as compared to the wild type (WT) receptor. Optimization of the aniline portion revealed s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Salvati ME,Balog A,Wei DD,Pickering D,Attar RM,Geng J,Rizzo CA,Hunt JT,Gottardis MM,Weinmann R,Martinez R

更新日期：2005-01-17 00:00:00

abstract：:To elucidate the inhibitory action of acetogenins, the most potent inhibitors of mitochondrial complex I, we synthesized an acetogenin analogue which possesses a ubiquinone ring (i.e., the physiological substrate of complex I) in place of the alpha,beta-unsaturated gamma-lactone ring of natural acetogenins, and named ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yabunaka H,Abe M,Kenmochi A,Hamada T,Nishioka T,Miyoshi H

更新日期：2003-07-21 00:00:00

abstract：:Based on previous modeling predictions, a series of (3-substituted-5-chloro-2-pyridinyl)guanidines have been designed with good potency and selectivity for urokinase-type plasminogen activator (uPA). Compound 36 has a K(i) of 0.17 microM and greater than 300-fold selectivity with respect to tPA and plasmin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Dickinson RP

更新日期：2002-01-21 00:00:00

abstract：:The synthesis and biological activity of a novel series of tricyclic retinoic acid receptor antagonists are described. These compounds bind with high affinity to the RARs and are potent antagonists of retinoid function in in vitro and in vivo systems. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vuligonda V,Standeven AM,Escobar M,Chandraratna RA

更新日期：1999-03-08 00:00:00

abstract：:Bisubstrate analog inhibitors in which a nicotinamide mimic is attached to a series of structurally diversified guanidines (arginine mimics) were synthesized and evaluated for inhibition of cholera toxin. The mechanism-based bisubstrate inhibitors were up to 1400-fold more potent than the natural substrate NAD+ and 40...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang G

更新日期：2008-07-01 00:00:00

abstract：:A novel solid-phase synthesis of 5'-radiolabeled oligonucleotides is described. The labeling reaction is carried out by the phosphoramidite method with the aid of [4,6-di-14C]-5'-dimethoxytritylthymidine building block 1. The feasibility of the method is demonstrated by preparation of 3'-phosphorylated dodecathymidyla...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guzaev A,Boyode B,Balow G,Tivel KL,Manoharan M

更新日期：1998-05-05 00:00:00

abstract：:A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jung MH,El-Gamal MI,Abdel-Maksoud MS,Sim T,Yoo KH,Oh CH

更新日期：2012-07-01 00:00:00

abstract：:The piperidyl and prolyl amides of Kemp's triacid (7 and 8, respectively) have been prepared and their rates of intramolecular acylolysis measured as a function of pD. The piperidyl derivative 7 reacts approximately four-times faster (e.g., t(1/2)=3 min at 20 degrees C and pD7.7) than the previously reported pyrrolidy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dougan ML,Chin JL,Solt K,Hansen DE

更新日期：2004-08-16 00:00:00

abstract：:This study explores the possible use of reactive oxygen-activated DNA modifying agents against acute myeloid leukemia (AML). A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds ha...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bell-Horwath TR,Vadukoot AK,Thowfeik FS,Li G,Wunderlich M,Mulloy JC,Merino EJ

更新日期：2013-05-15 00:00:00

abstract：:SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ishii H,Koyama H,Hagiwara K,Miura T,Xue G,Hashimoto Y,Kitahara G,Aida Y,Suzuki M

更新日期：2012-02-01 00:00:00

abstract：:A group of fluorophore-labeled peptide substrates of Src kinases have been synthesized with the aid of click chemistry. Some of the generated peptides exhibit an increase in fluorescence upon phosphorylation and are capable of detecting Src kinases with high sensitivity and specificity. Their availability permits real...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kamaruddin MA,Ung P,Hossain MI,Jarasrassamee B,O'Malley W,Thompson P,Scanlon D,Cheng HC,Graham B

更新日期：2011-01-01 00:00:00

abstract：:Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim. Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer. However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined. Thus, the cur...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu H,Yu X,Qu S,Sui D

更新日期：2013-06-15 00:00:00

abstract：:Four stereoisomeric hybrids of the polyketide natural products callystatin A and leptomycin B have been prepared by parallel synthetic routes involving chiral allenylstannane methodology. Like their natural counterparts, these hybrids exhibit nanomolar levels of cytotoxicity toward HCT-116 human colon cancer cells. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marshall JA,Mikowski AM,Bourbeau MP,Schaaf GM,Valeriote F

更新日期：2006-01-15 00:00:00

abstract：:We proposed a novel QSAR (quantitative structure-activity relationship) procedure called LERE (linear expression by representative energy terms)-QSAR involving molecular calculations such as ab initio fragment molecular orbital and generalized Born/surface area ones. We applied LERE-QSAR to two datasets for the free-e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Munei Y,Shimamoto K,Harada M,Yoshida T,Chuman H

更新日期：2011-01-01 00:00:00

abstract：:A novel class of 2,3-diaminopyridine bradykinin B1 receptor antagonists is disclosed. Structure-activity relationship studies (SARs) that led to compounds with significantly improved potency and pharmacokinetic properties relative to the lead compound are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Feng DM,Wai JM,Kuduk SD,Ng C,Murphy KL,Ransom RW,Reiss D,Chang RS,Harrell CM,MacNeil T,Tang C,Prueksaritanont T,Freidinger RM,Pettibone DJ,Bock MG

更新日期：2005-05-02 00:00:00

abstract：:A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups have been synthesized and their activities against HIV-1 and HIV-2 have been evaluated. Two trans isomers have been endowed with interesting antiviral properties, confirming the importance of the relative positions of the substituent on the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Marchesan S,Da Ros T,Spalluto G,Balzarini J,Prato M

更新日期：2005-08-01 00:00:00

abstract：:Reaction of 7-amino-9-ethylguaninium chloride with lead(IV) acetate (LTA) in MeOH yielded 8-aza-9-ethylguanine. Similarly, the reaction of 1-amino-3-methylbenzimidazolium chloride or its substituted derivatives (6-methyl, 5,6-dimethyl and 5-nitro) with LTA gave the corresponding 1-methyl-1H-benzotriazole (or 1-methyl-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaiya T,Aoyama S,Kohda K

更新日期：1999-04-05 00:00:00

abstract：:To improve the pharmacokinetics of a previously reported series of dipeptidyl nitrile cathepsin B inhibitors, the P(2)-P(3) amide group was replaced with an arylamine. Further optimization of this template resulted in highly potent and selective inhibitors with excellent oral availability. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Greenspan PD,Clark KL,Cowen SD,McQuire LW,Tommasi RA,Farley DL,Quadros E,Coppa DE,Du Z,Fang Z,Zhou H,Doughty J,Toscano KT,Wigg AM,Zhou S

更新日期：2003-11-17 00:00:00

abstract：:A series of N-7-methyl-imidazolopyrimidine inhibitors of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-methyl substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee W,Ortwine DF,Bergeron P,Lau K,Lin L,Malek S,Nonomiya J,Pei Z,Robarge KD,Schmidt S,Sideris S,Lyssikatos JP

更新日期：2013-09-15 00:00:00

abstract：:A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sharma VM,Adi Seshu KV,Vamsee Krishna C,Prasanna P,Chandra Sekhar V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Deevi DS,Rao Mamidi NV,Rajagopalan R

更新日期：2003-05-19 00:00:00

abstract：:In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Brabez N,Nguyen KL,Saunders K,Lacy R,Xu L,Gillies RJ,Lynch RM,Chassaing G,Lavielle S,Hruby VJ

更新日期：2013-04-15 00:00:00

abstract：:The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar ren...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lacombe P,Aspiotis R,Bayly C,Chen A,Dubé D,Fortin R,Gallant M,Juteau H,Liu S,McKay D,Roy P,Wu T

更新日期：2010-10-01 00:00:00

abstract：:Radioligands are powerful tools for examining the pharmacological profiles of chemical leads and thus facilitate drug discovery. In this study, we identified and characterized 3-([1,1,1-(3)H]methyl)-2-(4-{[3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone ([(3)H]1) as a potent and selective radioligand for his...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mitobe Y,Ito S,Mizutani T,Nagase T,Sato N,Tokita S

更新日期：2009-08-01 00:00:00

abstract：:A series of Sordarin derivatives bearing alkyl substituted tetrahydrofuran rings fused to C3'-C4' bond of the sugar moiety have been prepared and their antifungal properties evaluated. Most of them show remarkable antifungal activity against Candida spp and Cryptococcus neoformans. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bueno JM,Chicharro J,Fiandor JM,Gómez de las Heras F,Huss S

更新日期：2002-07-08 00:00:00

abstract：:Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-tar...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chen GL,Wang LH,Wang J,Chen K,Zhao M,Sun ZZ,Wang S,Zheng HL,Yang JY,Wu CF

更新日期：2013-07-01 00:00:00