Synthesis and properties of prodrugs activated in hypoxia to give bleomycin analogues.

abstract：:Several strychnobrasiline derivatives have been synthesized to overcome the lack of in vivo reversal activity of the parent compound. In the present study, N(a)-deacetyl-ferrocenoyl-strychnobrasiline was synthesized by condensing N(a)-deacetyl-strychnobrasiline with ferrocenic acid previously treated with oxalyl chlor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Razafimahefa D,Pélinski L,Martin MT,Ramanitrahasimbola D,Rasoanaivo P,Brocard J

更新日期：2005-02-15 00:00:00

abstract：:The synthesis of 3-deoxydihydrolycoricidine, a key element toward elucidation of the pancratistatin anticancer pharmacophore, is described. Biological evaluation of this compound showed it to be significantly less active against tumor cells than pancratistatin. In addition to those features previously identified, the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： McNulty J,Larichev V,Pandey S

更新日期：2005-12-01 00:00:00

abstract：:Recently, a new class of selective integrin alpha5beta1inhibitors consisting of a heterocyclic based scaffold was published. Herein the SAR and pharmacokinetic profiles of N-phenyl piperidine derivatives are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zischinsky G,Osterkamp F,Vossmeyer D,Zahn G,Scharn D,Zwintscher A,Stragies R

更新日期：2010-01-01 00:00:00

abstract：:MDM2 and MDMX are oncoproteins that negatively regulate the activity and stability of the tumor suppressor protein p53. The inhibitors of protein-protein interactions (PPIs) of MDM2-p53 and MDMX-p53 represent potential anticancer agents. In this study, a novel approach for identifying MDM2-p53 and MDMX-p53 PPI inhibit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Noguchi T,Oishi S,Honda K,Kondoh Y,Saito T,Kubo T,Kaneda M,Ohno H,Osada H,Fujii N

更新日期：2013-07-01 00:00:00

abstract：:Four platinum(II) complexes of N-cyclobutyl-1R,2R-diaminocyclohexane with different bidentate dicarboxylates (1 oxalate, 2 malonate, 3 1,1-cyclobutanedicarboxylate and 4 3-hydroxy-1,1-cyclobutanedicarboxylate) as leaving groups were synthesized and characterized by elemental analyses, IR and (1)HNMR spectra together w...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xu G,Zhao J,Gou S,Pang J

更新日期：2015-01-15 00:00:00

abstract：:We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved t...

journal_title：Bioorganic & medicinal chemistry letters

authors： McComas C,Cohen J,Huselton C,Marella M,Melenski E,Mugford C,Slayden O,Winneker R,Wrobel J,Yudt MR,Fensome A

更新日期：2012-12-01 00:00:00

abstract：:DNA binding ligands with potent antimicrobial activity against Gram-positive bacteria were further optimized by variation of the internal aromatic amino acids. This modification led to compounds with improved in vivo efficacy in lethal murine models of peritonitis (methicillin-resistant S. aureus, MRSA) and lung infec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bürli RW,Kaizerman JA,Duan JX,Jones P,Johnson KW,Iwamoto M,Truong K,Hu W,Stanton T,Chen A,Touami S,Gross M,Jiang V,Ge Y,Moser HE

更新日期：2004-05-03 00:00:00

abstract：:A new series of 3,3-disubstituted-5-aryloxindoles has been synthesized and evaluated for progesterone receptor antagonist (PR) activity in a T47D cell alkaline phosphatase assay and for their ability to bind PR in competition binding studies. In this communication, the synthesis and structure-activity relationships (S...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fensome A,Bender R,Cohen J,Collins MA,Mackner VA,Miller LL,Ullrich JW,Winneker R,Wrobel J,Zhang P,Zhang Z,Zhu Y

更新日期：2002-12-02 00:00:00

abstract：:Molecular modeling studies performed on the two cyclooxygenase (COX) isozymes suggest that the cavity at the mouth of the active site on the membrane domain that may act as an actual binding site of COX ligands. Actual docking of different inhibitors at this site provides a structural basis to explain the dynamics of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Llorens O,Perez JJ,Palomer A,Mauleon D

更新日期：1999-10-04 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：:Xanthorrhizol, isolated from the Indonesian Java turmeric Curcuma xanthorrhiza, displays broad-spectrum antibacterial activity. We report herein the evidence that mechanism of action of xanthorrhizol may involve FabI, an enoyl-(ACP) reductase, inhibition. The predicted Y156V substitution in the FabI enzyme promoted xa...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yogiara,Mordukhova EA,Kim D,Kim WG,Hwang JK,Pan JG

更新日期：2020-12-15 00:00:00

abstract：:Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50=8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor eff...

journal_title：Bioorganic & medicinal chemistry letters

authors： Aoki T,Hyohdoh I,Furuichi N,Ozawa S,Watanabe F,Matsushita M,Sakaitani M,Ori K,Takanashi K,Harada N,Tomii Y,Tabo M,Yoshinari K,Aoki Y,Shimma N,Iikura H

更新日期：2013-12-01 00:00:00

abstract：:The enzymatic synthesis of Gal-beta 1,3[GlcNAc-beta 1,6]-GalNAc-alpha 1-OBn (core 2-Bn) using a multi-enzyme system consisting of a beta-galactosidase (EC 3.2.1.23) from bovine testes and a recombinant core 2 beta 1,6-GlcNAc transferase (C2GnT, EC 2.4.1.102) was empirically optimized by the use of a genetic algorithm....

journal_title：Bioorganic & medicinal chemistry letters

authors： Hoh C,Dudziak G,Liese A

更新日期：2002-04-08 00:00:00

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：:Mass-guided fractionation of the MeOH extract from a specimen of the Australian marine sponge Hyrtios sp. resulted in the isolation of two new tryptophan alkaloids, 6-oxofascaplysin (2), and secofascaplysic acid (3), in addition to the known metabolites fascaplysin (1) and reticulatate (4). The structures of all molec...

journal_title：Bioorganic & medicinal chemistry letters

authors： Khokhar S,Feng Y,Campitelli MR,Ekins MG,Hooper JN,Beattie KD,Sadowski MC,Nelson CC,Davis RA

更新日期：2014-08-01 00:00:00

abstract：:As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qiao Z,Wang W,Wang L,Wen D,Zhao Y,Wang Q,Meng Q,Chen G,Wu Y,Zhou H

更新日期：2011-11-01 00:00:00

abstract：:A two-step reaction cascade is applied to the sequence-specific detection of single-stranded DNA, including analyte-triggered re-activation of apo-aldolase by its cofactor Zn(2+) and catalytic conversion of a chromophore. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Graf N,Kassube S,Krämer R

更新日期：2008-09-01 00:00:00

abstract：:Carbohydrate chip technology has a great potential for the high-throughput evaluation of carbohydrate-protein interactions. Herein, we report syntheses of novel sulfated oligosaccharides possessing heparin and heparan sulfate partial disaccharide structures, their immobilization on gold-coated chips to prepare array-t...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wakao M,Saito A,Ohishi K,Kishimoto Y,Nishimura T,Sobel M,Suda Y

更新日期：2008-04-01 00:00:00

abstract：:Structure-activity studies on the oxytocin antagonist 1 (L-371,257) have identified a new series of high affinity, receptor-selective OT antagonists in which the N-acetyl-4-piperidinyl ether terminus in 1 has been replaced with a 1-(aryl)ethoxy group. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kuo MS,Bock MG,Freidinger RM,Guidotti MT,Lis EV,Pawluczyk JM,Perlow DS,Pettibone DJ,Quigley AG,Reiss DR,Williams PD,Woyden CJ

更新日期：1998-11-03 00:00:00

abstract：:The Letter describes the preparation and characterization of a conjugate of isoniazid (INH) with magnetic nanoparticles Fe3O4@SiO2 115±60 nm in size. The INH molecules were attached to the surface of nanoparticles by a covalent pH-sensitive amidine bond. The conjugate was characterized by X-ray diffraction, SEM, dynam...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sedlák M,Bhosale DS,Beneš L,Palarčík J,Kalendová A,Královec K,Imramovský A

更新日期：2013-08-15 00:00:00

abstract：:The chemoenzymatic deacylation of ramoplanin A2 is described for the first time: ramoplanin A2 was Boc-protected and hydrogenated to Boc-protected tetrahydroramoplanin, which was subsequently deacylated using an acylase from Actinoplanes utahensis NRRL 12052. The chemoenzymatic process proceeded with 80% overall yield...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gandolfi R,Marinelli F,Ragg E,Romano D,Molinari F

更新日期：2012-08-15 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：:In our search for potent inhibitors of the enzyme estrone sulfatase (ES), we have undertaken the synthesis and biochemical evaluation of a range of straight chain alkyl esters of 4-[(aminosulfonyl)oxy] benzoic acid. The results of the study show that the synthesised compounds possess greater inhibitory activity when c...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ahmed S,James K,Owen CP

更新日期：2002-09-02 00:00:00

abstract：:A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that show...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kang IJ,Wang LW,Hsu SJ,Lee CC,Lee YC,Wu YS,Yueh A,Wang JC,Hsu TA,Chao YS,Chern JH

更新日期：2009-11-01 00:00:00

abstract：:A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang P,Terefenko EA,McComas CC,Mahaney PE,Vu A,Trybulski E,Koury E,Johnston G,Bray J,Deecher D

更新日期：2008-12-01 00:00:00

abstract：:A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sanner MA,Chappie TA,Dunaiskis AR,Fliri AF,Desai KA,Zorn SH,Jackson ER,Johnson CG,Morrone JM,Seymour PA,Majchrzak MJ,Faraci WS,Collins JL,Duignan DB,Prete Di CC,Lee JS,Trozzi A

更新日期：1998-04-07 00:00:00

abstract：:The synthesis of four new computer-designed fluoroquinolones which have been predicted by QSAR analysis to be active against the protozoa Toxoplasma gondii is described. These compounds are inhibitory in vitro for T. gondii. One of these compounds has a remarkably high activity comparable to that of trovafloxacin. It ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Anquetin G,Rouquayrol M,Mahmoudi N,Santillana-Hayat M,Gozalbes R,Greiner J,Farhati K,Derouin F,Guedj R,Vierling P

更新日期：2004-06-07 00:00:00

abstract：:5-Ethynyl-2'-deoxyuridine is a common base-modified nucleoside analogue that has served in various applications including selection experiments for potent aptamers and in biosensing. The synthesis of the corresponding triphosphates involves a mild acidic deprotection step. Herein, we show that this deprotection leads ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Röthlisberger P,Levi-Acobas F,Hollenstein M

更新日期：2017-02-15 00:00:00

abstract：:A series of genistein derivatives, prepared by alkylation and difluoromethylation, were tested for their inhibitory effects on the hydrogen peroxide induced impairment in human umbilical vein endothelial (HUVE-12) cells in vitro. The HUVE-12 cells were pretreated with either the vehicle solvent (DMSO), genistein, or d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fu XH,Wang L,Zhao H,Xiang HL,Cao JG

更新日期：2008-01-15 00:00:00

abstract：:The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Monte FL,Kramer T,Boländer A,Plotkin B,Eldar-Finkelman H,Fuertes A,Dominguez J,Schmidt B

更新日期：2011-09-15 00:00:00