Synthesis and evaluation of water-soluble docetaxel prodrugs-docetaxel esters of malic acid.

abstract：:2-Alkylamino-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydro-5-alkylpyrimidin-4(3H)-ones (F(2)-NH-DABOs) 4, 5 belonging to the dihydro-alkoxy-benzyl-oxopyrimidine (DABO) family and bearing different alkyl- and arylamino side chains at the C(2)-position of the pyrimidine ring were designed as active against wild type (wt) ...

journal_title：Bioorganic & medicinal chemistry

authors： Mai A,Artico M,Ragno R,Sbardella G,Massa S,Musiu C,Mura M,Marturana F,Cadeddu A,Maga G,La Colla P

更新日期：2005-03-15 00:00:00

abstract：:Reverse chemical proteomics using T7 phage display is a powerful technique for identifying cellular receptors of biologically active small molecules. However, to date this method has generally been limited to cDNA libraries constructed from mRNA isolated from eukaryotes. In this paper, we describe the construction of ...

journal_title：Bioorganic & medicinal chemistry

authors： Piggott AM,Kriegel AM,Willows RD,Karuso P

更新日期：2009-10-01 00:00:00

abstract：:The synthesis and optimization of a class of trisubstituted quinazoline-2,4(1H,3H)-dione cPLA(2)alpha inhibitors are described. Utilizing pharmacophores that were found to be important in our indole series, we discovered inhibitors with reduced lipophilicity and improved aqueous solubility. These compounds are active ...

journal_title：Bioorganic & medicinal chemistry

authors： Kirincich SJ,Xiang J,Green N,Tam S,Yang HY,Shim J,Shen MW,Clark JD,McKew JC

更新日期：2009-07-01 00:00:00

abstract：:There is still a need for additional scaffolds to further explore tissue selectivity and improving efficacy of selective estrogen receptor modulators (SERMs). A series of hydroxyl substituted diphenylnaphthyl alkene ligands for the two estrogen receptors are described that arose from an initial de novo designed diphen...

journal_title：Bioorganic & medicinal chemistry

authors： Schmidt JM,Tremblay GB,Plastina MA,Ma F,Bhal neé Basra S,Feher M,Dunn-Dufault R,Redden PR

更新日期：2005-03-01 00:00:00

abstract：:The intent of this investigation was to determine the effect of varying the side chain length of the basic amino acids residues on the binding of a series of antimicrobial peptides (AMPs) to zwitterionic and anionic LUVs, SUVs and micelles. These AMPs are based on the incorporation of three dipeptide units consisting ...

journal_title：Bioorganic & medicinal chemistry

authors： Russell AL,Williams BC,Spuches A,Klapper D,Srouji AH,Hicks RP

更新日期：2012-03-01 00:00:00

abstract：:A new class of compounds able to block the replication of subgenomic HCV RNA in liver cells is described. 3-Amino-2(5H)furanones 4 may be regarded as diketoacid analogues and were obtained by basic rearrangement of the isoxazolidine nucleus. ...

journal_title：Bioorganic & medicinal chemistry

authors： Iannazzo D,Piperno A,Romeo G,Romeo R,Chiacchio U,Rescifina A,Balestrieri E,Macchi B,Mastino A,Cortese R

更新日期：2008-11-01 00:00:00

abstract：:The problem of predicting torsadogenic cardiotoxicity of drugs is afforded in this work. QSAR studies on a series of molecules, acting as hERG K+ channel blockers, were carried out for this purpose by using the CODESSA program. Molecules belonging to the analyzed dataset are characterized by different therapeutic targ...

journal_title：Bioorganic & medicinal chemistry

authors： Coi A,Massarelli I,Murgia L,Saraceno M,Calderone V,Bianucci AM

更新日期：2006-05-01 00:00:00

abstract：:Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the f...

journal_title：Bioorganic & medicinal chemistry

authors： He W,Cik M,Van Puyvelde L,Van Dun J,Appendino G,Lesage A,Van der Lindin I,Leysen JE,Wouters W,Mathenge SG,Mudida FP,De Kimpe N

更新日期：2002-10-01 00:00:00

abstract：:Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid, 1), a naturally occurring neurotoxin isolated from Streptomyces toyocaenis, has been shown to be a mechanism-based inactivator of gamma-aminobutyric acid aminotransferase (GABA-AT) (Rando, R. R. Biochemistry 1977, 16, 4604). Inactivation results from reaction of ...

journal_title：Bioorganic & medicinal chemistry

authors： Fu M,Silverman RB

更新日期：1999-08-01 00:00:00

abstract：:Cytosporolide (Cytos) A-C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we...

journal_title：Bioorganic & medicinal chemistry

authors： Otake K,Yamada K,Miura K,Sasazawa Y,Miyazaki S,Niwa Y,Ogura A,Takao KI,Simizu S

更新日期：2019-08-01 00:00:00

abstract：:Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is recognized as an attractive target for the development of new agents for the treatment of influenza infection. Our earlier study employing small molecule fragment screening using a high-resolution crystal form of pandemic 2009 H1N1 in...

journal_title：Bioorganic & medicinal chemistry

authors： Parhi AK,Xiang A,Bauman JD,Patel D,Vijayan RS,Das K,Arnold E,Lavoie EJ

更新日期：2013-11-01 00:00:00

abstract：:omega-(1H-Imidazol-4-yl)alkane-1-sulfonamides were prepared and found to be potent histamine H(3) receptor antagonists. High receptor affinity and a low difference in the data between the bioassays were achieved with 5-(1H-imidazol-4-yl)pentane-1-sulfonic acid 4-chlorobenzylamide (16). Good in vitro profiles were also...

journal_title：Bioorganic & medicinal chemistry

authors： Tozer MJ,Buck IM,Cooke T,Kalindjian SB,Pether MJ,Steel KI

更新日期：2002-02-01 00:00:00

abstract：:Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series...

journal_title：Bioorganic & medicinal chemistry

authors： Liu J,Qian C,Zhu Y,Cai J,He Y,Li J,Wang T,Zhu H,Li Z,Li W,Hu L

更新日期：2018-02-01 00:00:00

abstract：:The synthesis and the binding study of new 3-arylesters and 3-heteroarylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide 8-substituted are reported. The nature of these substituents (in terms of lipophilic and electronic features) seems to influence the binding affinity. High-affinity ligands were studied in mice in vivo f...

journal_title：Bioorganic & medicinal chemistry

authors： Guerrini G,Costanzo A,Ciciani G,Bruni F,Selleri S,Costagli C,Besnard F,Costa B,Martini C,De Siena G,Malmberg-Aiello P

更新日期：2006-02-01 00:00:00

abstract：:The histamine H(3) receptor (H(3)R) plays a role in cognition and memory processes and is implicated in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. In vivo studies of the H(3)R occupancy using a radiolabeled PET tracer would be very useful for CNS drug discovery and ...

journal_title：Bioorganic & medicinal chemistry

authors： Selivanova SV,Honer M,Combe F,Isensee K,Stark H,Krämer SD,Schubiger PA,Ametamey SM

更新日期：2012-05-01 00:00:00

abstract：:Compounds from a wide variety of structural classes inhibit HIV-1 integrase. However, a single unified understanding of the relationship between the structures and activities of these compounds still eludes researchers. We report herein the development of QSAR models for integrase inhibition. The genetic function appr...

journal_title：Bioorganic & medicinal chemistry

authors： Yuan H,Parrill AL

更新日期：2002-12-01 00:00:00

abstract：:The human telomeric sequence d[AGGG(TTAGGG)(3)] has been found to form different types of G-quadruplex structures. NMR revealed that in Na(+) solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K(+) showed a dramatically different parallel s...

journal_title：Bioorganic & medicinal chemistry

authors： Xu Y,Noguchi Y,Sugiyama H

更新日期：2006-08-15 00:00:00

abstract：:Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II in...

journal_title：Bioorganic & medicinal chemistry

authors： Mollica A,Costante R,Akdemir A,Carradori S,Stefanucci A,Macedonio G,Ceruso M,Supuran CT

更新日期：2015-09-01 00:00:00

abstract：:Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charge...

journal_title：Bioorganic & medicinal chemistry

authors： Na H,Li X,Zou C,Wang C,Wang C,Liu K

更新日期：2016-07-01 00:00:00

abstract：:The success of inhibition of the proteasome by formation of covalent bonds is a major victory over the long held-view that this would lead to binding the wrong targets and undoubtedly lead to toxicity. Great challenges are now found in uncovering ensembles of new moieties capable of forming long lasting ties. We have ...

journal_title：Bioorganic & medicinal chemistry

authors： Brouwer AJ,Herrero Álvarez N,Ciaffoni A,van de Langemheen H,Liskamp RM

更新日期：2016-08-15 00:00:00

abstract：:Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

journal_title：Bioorganic & medicinal chemistry

authors： Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

更新日期：2010-03-01 00:00:00

abstract：:The synthesis and antitumoral activity of ester and amide derivatives of 2-arylamino-6-trifluoromethyl-3-pyridinecarboxylic acids 8-58 is described. Trifluoromethylpyridine derivatives 8-58 were evaluated for their anticancer activity toward human tumoral cell lines by the National Cancer Institute (NCI). Most of them...

journal_title：Bioorganic & medicinal chemistry

authors： Onnis V,Cocco MT,Lilliu V,Congiu C

更新日期：2008-03-01 00:00:00

abstract：:Formation of dinitrosyl iron complexes (DNICs) was observed in a wide spectrum of pathophysiological conditions associated with overproduction of NO. To gain insight into the possible genotoxic effects of DNIC, we examined the interaction of histidinyl dinitrosyl iron complexes (HIS-DNIC) with DNA by means of circular...

journal_title：Bioorganic & medicinal chemistry

authors： Lewandowska H,Stępkowski TM,Sadło J,Wójciuk GP,Wójciuk KE,Rodger A,Kruszewski M

更新日期：2012-11-15 00:00:00

abstract：:It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both i.v. and p.o. administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1, generated by human liver microsomes as 20a, a hydroxylated compound at the...

journal_title：Bioorganic & medicinal chemistry

authors： Takeda Y,Uoto K,Chiba J,Horiuchi T,Iwahana M,Atsumi R,Ono C,Terasawa H,Soga T

更新日期：2003-10-01 00:00:00

abstract：:Combinatorial biocatalysis, based on a principle of the combinatorial use of biosynthetic steps rather than the combinatorial use of reagents, offers a complementary approach to combinatorial chemistry, which, used individually or in connection with synthetic organic transformations, provides access to analogues not r...

journal_title：Bioorganic & medicinal chemistry

authors： Krstenansky JL,Khmelnitsky Y

更新日期：1999-10-01 00:00:00

abstract：:WAP-8294A2 is a cyclic peptide antibiotic with novel structure and excellent activity against Gram-positive pathogens. Herein, we report the total synthesis of complex macrocyclic peptide WAP-8294A2 (W1), ent-analogue W2, deoxy analogue W3 and de-methyl analogue W4 using a solid-phase synthetic route followed by a fin...

journal_title：Bioorganic & medicinal chemistry

authors： Chen D,Tian L,Po KHL,Chen S,Li X

更新日期：2020-09-15 00:00:00

abstract：:A regioselective synthesis of 2,3-disubstituted tetrahydro-2H-indazols, mediated by alpha-zirconium sulfophenylphosphonate-methanephosphonate, was reported. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. Two lead derivatives were chosen endowed with g...

journal_title：Bioorganic & medicinal chemistry

authors： Rosati O,Curini M,Marcotullio MC,Macchiarulo A,Perfumi M,Mattioli L,Rismondo F,Cravotto G

更新日期：2007-05-15 00:00:00

abstract：:Polymeric nanoparticles (NPs) comprised of hydrophilic poly(γ-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (γ-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered γ-PGA-Phe NPs. Therefore, we n...

journal_title：Bioorganic & medicinal chemistry

authors： Toita R,Kanai Y,Watabe H,Nakao K,Yamamoto S,Hatazawa J,Akashi M

更新日期：2013-09-01 00:00:00

abstract：:A series of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes were prepared and evaluated for affinities at dopamine, serotonin, and norepinephrine transporters using competitive radioligand binding assays. The 2beta-[3'-(substit...

journal_title：Bioorganic & medicinal chemistry

authors： Jin C,Navarro HA,Page K,Carroll FI

更新日期：2008-07-15 00:00:00

abstract：:4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologi...

journal_title：Bioorganic & medicinal chemistry

authors： Matulenko MA,Lee CH,Jiang M,Frey RR,Cowart MD,Bayburt EK,Didomenico S,Gfesser GA,Gomtsyan A,Zheng GZ,McKie JA,Stewart AO,Yu H,Kohlhaas KL,Alexander KM,McGaraughty S,Wismer CT,Mikusa J,Marsh KC,Snyder RD,Diehl MS,

更新日期：2005-06-01 00:00:00