Discovery and optimization of novel constrained pyrrolopyridone BET family inhibitors.

abstract：:Amide- and ester-linked kinase inhibitor-cytotoxin conjugates were rationally designed and synthesised as prototype hypoxia-activated anticancer mutual prodrugs. Chemical reduction of an aryl nitro trigger moiety was shown to initiate a spontaneous cyclisation/fragmentation reaction that simultaneously released the ki...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sansom GN,Kirk NS,Guise CP,Anderson RF,Smaill JB,Patterson AV,Kelso MJ

更新日期：2019-05-15 00:00:00

abstract：:The increase in the prevalence of multi drug-resistant and extensively drug-resistant strains of Mycobacteriumtuberculosis case demonstrates the urgent need of discovering new promising compounds with antimycobacterial activity. As part of our research program and with a aim of identifying new antitubercular drug cand...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alegaon SG,Alagawadi KR,Sonkusare PV,Chaudhary SM,Dadwe DH,Shah AS

更新日期：2012-03-01 00:00:00

abstract：:A cyclic imine conjugated to a fluorescent dansyl group was synthesized and used for covalent labeling of proteins. The covalent attachment to proteins was confirmed by gel electrophoresis and mass analysis. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo HM,Minakawa M,Ueno L,Tanaka F

更新日期：2009-02-15 00:00:00

abstract：:A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Faria JV,dos Santos MS,Bernardino AM,Becker KM,Machado GM,Rodrigues RF,Canto-Cavalheiro MM,Leon LL

更新日期：2013-12-01 00:00:00

abstract：:A 1,8-naphthalimide-Cu(II) ensemble was rationally designed and synthesized as a new turn-on fluorescent probe utilizing the 'chemosensing ensemble' method for detections of thiols (Cys, Hcy and GSH) with high selectivity over other α-amino acids at pH 7.4 in organic aqueous media (EtOH/HEPES, v/v=9:1). The recognitio...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi YG,Yao JH,Duan YL,Mi QL,Chen JH,Xu QQ,Gou GZ,Zhou Y,Zhang JF

更新日期：2013-05-01 00:00:00

abstract：:New 4-anilidopiperidine analogues in which the phenethyl group of fentanyl was replaced by several aromatic ring-contained amino acids (or acids) were synthesized to study the biological effect of the substituents on mu and delta opioid receptor interactions. These analogues showed broad (47 nM-76 microM) but selectiv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee YS,Nyberg J,Moye S,Agnes RS,Davis P,Ma SW,Lai J,Porreca F,Vardanyan R,Hruby VJ

更新日期：2007-04-15 00:00:00

abstract：:A series of acetylenic chalcones were evaluated for antimalarial and antitubercular activity. The antimalarial data for this series suggests that growth inhibition of the W2 strain of Plasmodium falciparum can be imparted by the introduction of a methoxy group ortho to the acetylenic group. Most compounds were more ac...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hans RH,Guantai EM,Lategan C,Smith PJ,Wan B,Franzblau SG,Gut J,Rosenthal PJ,Chibale K

更新日期：2010-02-01 00:00:00

abstract：:The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6'-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dini C,Didier-Laurent S,Drochon N,Feteanu S,Guillot JC,Monti F,Uridat E,Zhang J,Aszodi J

更新日期：2002-04-22 00:00:00

abstract：:To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluation...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lu XF,Yang Z,Huang NY,He HB,Deng WQ,Zou K

更新日期：2015-09-01 00:00:00

abstract：:Pyridone-based peptidomimetic inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with an aminomethylene ketone activating group in the P1' position are described. Several analogues with sub-nanomolar Ki's versus ICE and improved aqueous solubility are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Semple G,Ashworth DM,Batt AR,Baxter AJ,Benzies DW,Elliot LH,Evans DM,Franklin RJ,Hudson P,Jenkins PD,Pitt GR,Rooker DP,Yamamoto S,Isomura Y

更新日期：1998-04-21 00:00:00

abstract：:A new class of inhibitors of HIV-1 integrase has been optimized to provide selective and highly efficient strand transfer inhibition. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Donghi M,Kinzel OD,Summa V

更新日期：2009-04-01 00:00:00

abstract：:Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family bearing a p-alkylphenyl side chain have been synthesised and tested for their antiviral activity against Varicella-Zoster virus (VZV). While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Angell A,McGuigan C,Garcia Sevillano L,Snoeck R,Andrei G,De Clercq E,Balzarini J

更新日期：2004-05-17 00:00:00

abstract：:Piperazinyl benzamidines were prepared and found to bind to the rat delta (delta) opioid receptor. The most active compounds had a N,N-diethylcarboxamido group and a N-benzyl piperazine. The most potent among these was N,N-diethyl-4-[4-(phenylmethyl)-1-piperazinyl][2-(trifluoromethyl)phenyl]iminomethyl]benzamide (27) ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nortey SO,Baxter EW,Codd EE,Zhang SP,Reitz AB

更新日期：2001-07-09 00:00:00

abstract：:A protocol applicable for the synthesis of an oseltamivir positron emission tomography (PET) tracer was developed. Acetylation of amine 3 with CH(3)COCl, followed by deprotection and aqueous workup, produced oseltamivir 4 from 3 within 10 min. The obtained 4 was sufficiently pure for PET studies. This method can be ex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Morita M,Sone T,Yamatsugu K,Sohtome Y,Matsunaga S,Kanai M,Watanabe Y,Shibasaki M

更新日期：2008-01-15 00:00:00

abstract：:There is a great urgency in developing a new generation of antibiotics and antimicrobial agents since the bacterial resistance to antibiotics have increased dramatically. A series of overlapped peptide fragments of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, was des...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wu YS,Liao ZJ,Wang KS,Lung FD

更新日期：2013-05-15 00:00:00

abstract：:The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buckman BO,Mohan R,Koovakkat S,Liang A,Trinh L,Morrissey MM

更新日期：1998-08-18 00:00:00

abstract：:PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody dr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Holte D,Lyssikatos JP,Valdiosera AM,Swinney Z,Sisodiya V,Sandoval J,Lee C,Aujay MA,Tchelepi RB,Hamdy OM,Gu C,Lin B,Sarvaiya H,Pysz MA,Laysang A,Williams S,Jun Lee D,Holda MK,Purcell JW,Gavrilyuk J

更新日期：2020-12-15 00:00:00

abstract：:A novel diamino-substituted hypocrellin derived from hypocrellin B (HB) was synthesized by a mild method. The red absorption of the resulting product was significantly enhanced relative to the parent hypocrellins and any other hypocrellin derivatives, and the active oxygen species generating abilities were enhanced di...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu S,Chen S,Zhang M,Shen T

更新日期：2004-03-22 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：:The synthesis and pharmacological evaluation of substituted oximino-ethers 1 and 2 of naphth[1,2-b]- and naphth[2,1-b]-oxepin-5-ones (4 and 8) were carried out. The hypotensive activity of oximino-ethers 1 and 2 was evaluated on anaesthetized cats. The results indicated that 1c caused a fall of 80 mm/Hg for >100' at a...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tandon VK,Kumar M,Awasthi AK,Saxena HO,Goswamy GK

更新日期：2004-06-21 00:00:00

abstract：:The synthesis and biological activity of amino acid functionalized beta-carboline derivatives, which are structurally related to azatoxin and the tryprostatins, are reported. These compounds were assayed for their growth inhibition properties in H520 and PC3 cell lines and were examined for their abilities to inhibit ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deveau AM,Labroli MA,Dieckhaus CM,Barthen MT,Smith KS,Macdonald TL

更新日期：2001-05-21 00:00:00

abstract：:Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ghosh AK,Kumaragurubaran N,Hong L,Kulkarni S,Xu X,Miller HB,Reddy DS,Weerasena V,Turner R,Chang W,Koelsch G,Tang J

更新日期：2008-02-01 00:00:00

abstract：:A series of 1-indazol-3-(1-phenylpyrazol-5-yl)methyl ureas were investigated as hTRPV1 antagonists. The structure-activity relationship study was conducted systematically for both the indazole A-region and the 3-trifluoromethyl/t-butyl pyrazole C-region to optimize the antagonism toward the activation by capsaicin. Am...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang JM,Kwon SO,Ann J,Blumberg PM,Ha H,Yoo YD,Frank-Foltyn R,Lesch B,Bahrenberg G,Stockhausen H,Christoph T,Lee J

更新日期：2020-12-01 00:00:00

abstract：:By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 μM; MIC = 0.48 μM) than the positive controls AHA (IC50 = 17.2 μM) and Metronidazole (MIC = 31.3 ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang YS,Su MM,Zhang XP,Liu QX,He ZX,Xu C,Zhu HL

更新日期：2018-10-15 00:00:00

abstract：:In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0μM and no sign...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu HW,Zhao LJ,Liu HF,Zhao D,Luo J,Xie XP,Liu WS,Zheng JX,Dai GF,Liu HM,Liu LH,Liang YB

更新日期：2014-05-15 00:00:00

abstract：:A series of N-4-substituted-benzyl-N'-tert-butylbenzyl thioureas were prepared for the study of their agonistic/antagonistic activities to the vanilloid receptor in rat DRG neurons. Their structure-activity relationship reveals that not only the two oxygens and amide hydrogen of sulfonamido group, but also the optimal...

journal_title：Bioorganic & medicinal chemistry letters

authors： Park HG,Choi JY,Choi SH,Park MK,Lee J,Suh YG,Cho H,Oh U,Lee J,Kang SU,Lee J,Kim HD,Park YH,Su Jeong Y,Kyu Choi J,Jew SS

更新日期：2004-02-09 00:00:00

abstract：:Several recent reports have highlighted the feasibility of the use of penfluridol, a well-known antipsychotic agent, as a chemotherapeutic agent. In vivo experiments have confirmed the cytotoxic activity of penfluridol in triple-negative breast cancer model, lung cancer model, and further studies have been proposed to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ashraf-Uz-Zaman M,Sajib MS,Cucullo L,Mikelis CM,German NA

更新日期：2018-12-15 00:00:00

abstract：:KIAA1363 is a serine hydrolase whose activity has been shown to be positively associated with tumor cell invasiveness. Thus, inhibitors of KIAA1363 represent a novel targeted therapy approach towards cancer. AX11890 ((1-bromo-2-naphthyl) N,N-dimethylcarbamate) was identified as a KIAA1363 inhibitor with an IC(50) valu...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shreder KR,Lin EC,Wu J,Cajica J,Amantea CM,Hu Y,Okerberg E,Brown HE,Pham LM,Chung de M,Fraser AS,McGee E,Rosenblum JS,Kozarich JW

更新日期：2012-09-01 00:00:00

abstract：:Knoevenagel condensation was employed to generate a set of molecules potentially capable of inhibiting the RNA polymerase-σ70/σA interaction in bacteria. Synthesis was achieved via reactions between a variety of indole-7-carbaldehydes and rhodanine, N-allylrhodanine, barbituric acid or thiobarbituric acid. A library o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wenholz DS,Zeng M,Ma C,Mielczarek M,Yang X,Bhadbhade M,Black DSC,Lewis PJ,Griffith R,Kumar N

更新日期：2017-09-15 00:00:00

abstract：:The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reactin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang Z,Fang Z,He W,Wang Z,Gan H,Tian Q,Guo K

更新日期：2016-04-01 00:00:00