abstract：:The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao DG,Ma YY,Peng W,Zhou AY,Zhang Y,Ding L,Du Z,Zhang K

更新日期：2016-01-01 00:00:00

abstract：:The paper will describe the synthesis and SAR studies that led to the discovery of benzamide (reverse amide) as potent and selective human β3-adrenergic receptor agonist. Based on conformationally restricted pyrrolidine scaffold we discovered earlier, pyrrolidine benzoic acid intermediate 22 was synthesized. From libr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu C,Kar NF,Li B,Costa M,Dingley KH,Di Salvo J,Ha SN,Hurley AL,Li X,Miller RR,Salituro GM,Struthers M,Weber AE,Hale JJ,Edmondson SD

更新日期：2016-01-01 00:00:00

abstract：:In plant biology, calcium ions are involved in a variety of intriguing biological phenomena as a secondary messenger. However, most conventional calcium indicators are not applicable for plant cells because of the difficulty with their localization control in plant cells. We here introduce a method to monitor spatiote...

journal_title：Bioorganic & medicinal chemistry letters

authors： Takaoka Y,Shigenaga M,Imai M,Nukadzuka Y,Ishimaru Y,Saito K,Yokoyama R,Nishitani K,Ueda M

更新日期：2016-01-01 00:00:00

abstract：:A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kumar A,Qayum A,Sharma PR,Singh SK,Shah BA

更新日期：2016-01-01 00:00:00

abstract：:Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nakano H,Hasegawa T,Saito N,Furukawa K,Mukaida N,Kojima H,Okabe T,Nagano T

更新日期：2015-12-15 00:00:00

abstract：:5-Methylcytosine (5mC) is oxidized by ten-eleven translocation (TET) enzymes. This process followed by thymine DNA glycosylase is proposed to be the mechanism for methylcytosine demethylation. 5-Hydroxymethylcytosine (5hmC) is one of the most important key oxidative metabolites in the demethylation process, and theref...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fukuzawa S,Tachibana K,Tajima S,Suetake I

更新日期：2015-12-15 00:00:00

abstract：:Benzo[7]annulen-7-amines 7 without further polar substituents have been reported as conformationally restricted Ro 25-6981 analogs and show unexpectedly high GluN2B affinity. Herein the corresponding 2-NO2 derivatives 8 were synthesized and pharmacologically evaluated. NO2 derivatives 8 show 5- to 10-fold higher GluN2...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gawaskar S,Schepmann D,Bonifazi A,Robaa D,Sippl W,Wünsch B

更新日期：2015-12-15 00:00:00

abstract：:To identify small molecule inhibitors of TNF-α, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Khan R,Basha A,Goverdhanam R,Rao PC,Tanemura Y,Fujimoto Y,Begum AS

更新日期：2015-12-15 00:00:00

abstract：:Compound rac-1 was identified by high throughput screening. Here we report SAR studies and MedChem optimization towards the highly potent dual orexin receptor antagonists (S)-2 and (S)-3. Furthermore, strategies to overcome the suboptimal physicochemical properties are highlighted and the pharmacokinetic profiles of r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Behnke D,Cotesta S,Hintermann S,Fendt M,Gee CE,Jacobson LH,Laue G,Meyer A,Wagner T,Badiger S,Chaudhari V,Chebrolu M,Pandit C,Hoyer D,Betschart C

更新日期：2015-12-01 00:00:00

abstract：:Derivatives of phaeosphaeride A (PPA) were synthesised and characterised; then anti-cancer studies were carried out on the A549 cancer cell line. It was found that the acetyl derivative (compound 3) displayed comparable in vitro cytotoxicity to that of PPA (EC50=49±7 μM and EC50=46±5 μM, respectively), while chloroace...

journal_title：Bioorganic & medicinal chemistry letters

authors： Abzianidze VV,Prokofieva DS,Chisty LA,Bolshakova KP,Berestetskiy AO,Panikorovskii TL,Bogachenkov AS,Holder AA

更新日期：2015-12-01 00:00:00

abstract：:Cyclic azobenzene carboxylic acid was synthesized using a shortened route. After reaction with D-threolinol, the resulting cyclic azobenzene-D-threolinol (cAB-Thr) building block was transformed into the corresponding DMTr-protected phosphoramidite, and incorporated into oligodeoxynucleotides at various positions and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Eljabu F,Dhruval J,Yan H

更新日期：2015-12-01 00:00:00

abstract：:Novel ethynylphenyl carbonates and carbamates containing carbon- and silicon-based choline mimics were synthesized from their respective phenol and aniline precursors and screened for anticholinesterase and anti-inflammatory activities. All molecules were micromolar inhibitors of acetylcholinesterase (AChE), with IC50...

journal_title：Bioorganic & medicinal chemistry letters

authors： Saxena J,Meloni D,Huang MT,Heck DE,Laskin JD,Heindel ND,Young SC

更新日期：2015-12-01 00:00:00

abstract：:Cynaropicrin is a guaianolide sesquiterpene lactone, which has potent in vitro and in vivo inhibitory activity against Trypanosoma brucei, the protozoan parasite that causes human African trypanosomiasis (HAT; sleeping sickness). Herein, we describe the synthesis of cynaropicrin's deuterated derivative, cynaropicrin-d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sato T,Hara S,Sato M,Ogawa K,Adams M,Usuki T

更新日期：2015-12-01 00:00:00

abstract：:IRAK4 plays a critical role in the IL-1R and TLR signalling, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of permeable N-(1H-pyrazol-4-yl)carboxamides was developed by introducing lipophilic bicyclic cores in place o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lim J,Altman MD,Baker J,Brubaker JD,Chen H,Chen Y,Kleinschek MA,Li C,Liu D,Maclean JK,Mulrooney EF,Presland J,Rakhilina L,Smith GF,Yang R

更新日期：2015-11-15 00:00:00

abstract：:This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seo WD,Lee JH,Jia Y,Wu C,Lee SJ

更新日期：2015-11-15 00:00:00

abstract：:A series of pethidine analogs were synthesized and their affinities for the [(3)H]N-methyl-scopolamine (NMS) binding site on muscarinic acetylcholine receptors (mAChRs) were determined using M1, M3 or M5 human mAChRs expressed by Chinese hamster ovary (CHO) cell membranes. Compound 6b showed the highest binding affini...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee NR,Zhang X,Darna M,Dwoskin LP,Zheng G

更新日期：2015-11-15 00:00:00

abstract：:A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed an...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li D,Gao N,Zhu N,Lin Y,Li Y,Chen M,You X,Lu Y,Wan K,Jiang JD,Jiang W,Si S

更新日期：2015-11-15 00:00:00

abstract：:The discovery of a novel class of HCV inhibitors is described. The new amidinourea compounds were designed as isosteric analogues of the antiviral drug moroxydine. The two derivatives 11g and 11h showed excellent HCV inhibition activity and viability and proved to inhibit a step(s) of the RNA replication. The new comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Magri A,Reilly R,Scalacci N,Radi M,Hunter M,Ripoll M,Patel AH,Castagnolo D

更新日期：2015-11-15 00:00:00

abstract：:The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A rec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang L,Zhang W,Zhang X,Yin L,Chen B,Song J

更新日期：2015-11-15 00:00:00

abstract：:Selective estrogen receptor degraders (SERDs) have shown promise for the treatment of ER+ breast cancer. Disclosed herein is the continued optimization of our indazole series of SERDs. Exploration of ER degradation and antagonism in vitro followed by in vivo antagonism and oral exposure culminated in the discovery of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Govek SP,Nagasawa JY,Douglas KL,Lai AG,Kahraman M,Bonnefous C,Aparicio AM,Darimont BD,Grillot KL,Joseph JD,Kaufman JA,Lee KJ,Lu N,Moon MJ,Prudente RY,Sensintaffar J,Rix PJ,Hager JH,Smith ND

更新日期：2015-11-15 00:00:00

abstract：:Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazoline core to selectively inhibit EGFR/HER2 tyrosine kinases. Twel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elkamhawy A,Farag AK,Viswanath AN,Bedair TM,Leem DG,Lee KT,Pae AN,Roh EJ

更新日期：2015-11-15 00:00:00

abstract：:A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs...

journal_title：Bioorganic & medicinal chemistry letters

authors： Huang J,Liu H,Liu M,Zhang R,Li L,Wang B,Wang M,Wang C,Lu Y

更新日期：2015-11-15 00:00:00

abstract：:β-Sitosterol is the most abundant plant sterol in the human diet. It is also the major component of several traditional medicines, including saw palmetto and devil's claw. Although β-sitosterol is effective against enlarged prostate in human clinical trials and has anti-cancer and anti-inflammatory activities, the mec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lomenick B,Shi H,Huang J,Chen C

更新日期：2015-11-01 00:00:00

abstract：:Transglutaminase 2 (TG2) is a ubiquitously expressed, Ca(2+)-activated extracellular enzyme in mammals that is maintained in a catalytically dormant state by multiple mechanisms. Although its precise physiological role in the extracellular matrix remains unclear, aberrantly up-regulated TG2 activity is a hallmark of s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yi MC,Palanski BA,Quintero SA,Plugis NM,Khosla C

更新日期：2015-11-01 00:00:00

abstract：:In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP+HS IC50=0.67 nM), and selective compound (hERG IC50=19 μM) with favorable rodent...

journal_title：Bioorganic & medicinal chemistry letters

authors： Crowley BM,Stump CA,Nguyen DN,Potteiger CM,McWherter MA,Paone DV,Quigley AG,Bruno JG,Cui D,Culberson JC,Danziger A,Fandozzi C,Gauvreau D,Kemmerer AL,Menzel K,Moore EL,Mosser SD,Reddy V,White RB,Salvatore CA,Kane S

更新日期：2015-11-01 00:00:00

abstract：:Sphingosine-1-phosphate (S1P) is a ubiquitous, endogenous small molecule that is synthesized by two isoforms of sphingosine kinase (SphK1 and 2). Intervention of the S1P signaling pathway has attracted significant attention because alteration of S1P levels is linked to several disease states including cancer, fibrosis...

journal_title：Bioorganic & medicinal chemistry letters

authors： Congdon MD,Childress ES,Patwardhan NN,Gumkowski J,Morris EA,Kharel Y,Lynch KR,Santos WL

更新日期：2015-11-01 00:00:00

abstract：:Chemoselective purification technologies have seen great success in biomolecule isolation, with a classic example being the genetically-encoded His tag utilized to enrich desired proteins from a crude lysate. We sought to translate this purification tactic into a powerful tool for the isolation of natural products and...

journal_title：Bioorganic & medicinal chemistry letters

authors： Trader DJ,Carlson EE

更新日期：2015-11-01 00:00:00

abstract：:Tuberculosis (TB) continues to remain one of the most threatening diseases in the world. With the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) strains, the need to develop new therapies is dire. The syntheses of a focused library of hydroxamates and hydroxamic acids is described, as wel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Majewski MW,Cho S,Miller PA,Franzblau SG,Miller MJ

更新日期：2015-11-01 00:00:00

abstract：:In search of effective antidiabetic agents having therapeutic effect by inhibiting α-glucosidase and preventive effect by scavenging free radicals, Horsfieldia macrobotrys showed promising bioactivity required for the proposed criteria. Bioassay-guided isolation of the stem bark extract resulted in two new arylalkanon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramadhan R,Phuwapraisirisan P

更新日期：2015-10-15 00:00:00

abstract：:A one step synthesis of fluorescent 8-aryl-(7-deazaguanines) has been accomplished. Probes exhibit blue to green high quantum yield fluorescence in a variety of organic and aqueous solutions, high extinction coefficients, and large Stokes shifts often above 100 nm. The probes are highly cell permeable, and exhibit sta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dhimitruka I,Eubank TD,Gross AC,Khramtsov VV

更新日期：2015-10-15 00:00:00

abstract：:The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this gener...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sun W,Chu T

更新日期：2015-10-15 00:00:00

abstract：:Three groups of non-camptothecin compounds with four to five fused rings have been designed and synthesized. Their in vitro anti-proliferative activity has been evaluated with five different cancer cell lines (HCT116, PC3, U87MG, HepG2, SK-OV-3). Compounds B-2 and B-3 showed the most potent cell growth inhibition with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang C,Li S,Ji L,Liu S,Li Z,Li S,Meng X

更新日期：2015-10-15 00:00:00

abstract：:Some ergostane triterpenoids from Taiwanofungus camphoratus have been shown to exhibit anti-inflammatory activity in vitro. However, the effect of ergostane triterpenoids on the immune response remains unknown. In this study, we elucidated that ergostane triterpenoids significantly decreased the cytokines and chemokin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lin MK,Lee MS,Chang WT,Chen HY,Chen JF,Li YR,Lin CC,Wu TS

更新日期：2015-10-15 00:00:00

abstract：:The authentic standard PBB3 and its precursor N-desmethyl-PBB3 as well as TBS-protected N-desmethyl-PBB3 precursor for radiolabeling were synthesized from 5-bromo-2-nitropyridine, acrolein diethyl acetal, 6-methoxy-2-methylbenzothiazole, and diethylchlorophosphate with overall chemical yield 1% in six steps, 2% in fiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Xu Z,Zheng QH

更新日期：2015-10-15 00:00:00

abstract：:We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sagar SR,Agarwal JK,Pandya DH,Dash RP,Nivsarkar M,Vasu KK

更新日期：2015-10-15 00:00:00

abstract：:A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramírez-Cisneros MÁ,Rios MY,Aguilar-Guadarrama AB,Rao PP,Aburto-Amar R,Rodríguez-López V

更新日期：2015-10-15 00:00:00

abstract：:Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimida...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zawawi NK,Rajput SA,Taha M,Ahmat N,Ismail NH,Abdullah N,Khan KM,Choudhary MI

更新日期：2015-10-15 00:00:00

abstract：:Serine racemase, the enzyme responsible for d-serine synthesis in the central nervous system, has been identified as a potential therapeutic target to treat N-methyl-d-aspartate receptors-related pathologies. The search for specific inhibitors of the enzyme has revealed that serine racemase is a difficult target, with...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dellafiora L,Marchetti M,Spyrakis F,Orlandi V,Campanini B,Cruciani G,Cozzini P,Mozzarelli A

更新日期：2015-10-01 00:00:00

abstract：:A new series of triazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids (6a-s, 7a) were designed by a molecular hybridisation approach and the target molecules were synthesized via one pot click chemistry protocol. All the intermediates and final molecules were characterised using spectral methods and one of the target comp...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ramprasad J,Nayak N,Dalimba U,Yogeeswari P,Sriram D

更新日期：2015-10-01 00:00:00

abstract：:A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone template gave compounds with similar potency but allowed selectivity to be...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chapman TM,Wallace C,Gillen KJ,Bakrania P,Khurana P,Coombs PJ,Fox S,Bureau EA,Brownlees J,Melton DW,Saxty B

更新日期：2015-10-01 00:00:00