Abstract：
:For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC(50) of 6.8, 2.0, and 12 microM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Neyts J,De Clercq E,Singha R,Chang YH,Das AR,Chakraborty SK,Hong SC,Tsay SC,Hsu MH,Hwu JRdoi
10.1021/jm801240dsubject
Has Abstractpub_date
2009-03-12 00:00:00pages
1486-90issue
5eissn
0022-2623issn
1520-4804pii
10.1021/jm801240djournal_volume
52pub_type
杂志文章abstract：:Anthrax lethal factor (LF) is a critical virulence factor in the pathogenesis of anthrax. A structure-activity relationship (SAR) of potential lethal factor inhibitors (LFi) is presented in which the zinc-binding group (ZBG), linker, and backbone moieties for a series of hydroxypyrone-based compounds were systematical...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8013212
更新日期：2009-02-26 00:00:00
abstract：:The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00376a003
更新日期：1984-10-01 00:00:00
abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9014179
更新日期：2010-07-22 00:00:00
abstract：:The potencies of a series of 2 beta-substituted cocaine analogues to displace [3H]-3 beta-(p-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester binding in rat striatal membranes demonstrate the requirement for a 2 beta-substituent with two hydrogen-bond acceptors. The insensitivity of the ester moiety to steric ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00079a017
更新日期：1992-01-01 00:00:00
abstract：:Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201510p
更新日期：2012-02-09 00:00:00
abstract：:Pleuromutilin is an antibiotic that binds to bacterial ribosomes and thereby inhibit protein synthesis. A new series of semisynthetic pleuromutilin derivatives were synthesized by a click chemistry strategy. Pleuromutilin was conjugated by different linkers to a nucleobase, nucleoside, or phenyl group, as a side-chain...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201266b
更新日期：2012-03-08 00:00:00
abstract：:The p38 mitogen-activated protein (MAP) kinase has been implicated in the proinflammatory cytokine signal pathway, and its inhibitors are potentially useful for the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease. To develop a new drug for RA, we synthesized ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050165o
更新日期：2005-09-22 00:00:00
abstract：:3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00220a021
更新日期：1977-10-01 00:00:00
abstract：:A three-dimensional model of the AT1 receptor was constructed by means of a homology modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template and taking into account the available site-directed mutagenesis data. The docking of losartan and its active metabolite EXP3174, followed by 1 n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060338p
更新日期：2006-07-13 00:00:00
abstract：:Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1007209
更新日期：2010-11-11 00:00:00
abstract：:Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01605
更新日期：2015-11-12 00:00:00
abstract：:A series of 2'- and 3'-fluorinated 2',3'-dideoxynucleosides and 3'-azido-2',3'-dideoxynucleosides were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus-1 (HIV-1) replication in MT-4 cells. Neither conversion of 3'-fluoro- or 3'-azido-2',3'-dideoxyadenosine to the correspondi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a013
更新日期：1989-08-01 00:00:00
abstract：:Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980118e
更新日期：1998-11-19 00:00:00
abstract：:Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401389u
更新日期：2013-11-14 00:00:00
abstract：:Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00152a022
更新日期：1986-02-01 00:00:00
abstract：:DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00154a024
更新日期：1986-04-01 00:00:00
abstract：:A variety of sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. Several studies have shown that they exert this effect in part by inhibiting the activation of the transcription factor NF-kappaB. In the present study we elaborated on the investigation of a data set of 103 structurally diverse...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051125n
更新日期：2006-04-06 00:00:00
abstract：:The synthesis and evaluation of a refined series of alpha-ketoheterocycles based on the oxazole 2 (OL-135) incorporating systematic changes in the central heterocycle bearing a key set of added substituents are described. The nature of the central heterocycle, even within the systematic and minor perturbations explore...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800136b
更新日期：2008-08-14 00:00:00
abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00004a008
更新日期：1995-02-17 00:00:00
abstract：:We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized int...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970590k
更新日期：1998-01-01 00:00:00
abstract：:The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990159q
更新日期：1999-09-23 00:00:00
abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901872v
更新日期：2010-05-13 00:00:00
abstract：:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030549j
更新日期：2004-06-03 00:00:00
abstract：:For a fourth approach of quinoxaline N,N'-dioxides as anti-trypanosomatid agents against T. cruzi and Leishmania, we found extremely active derivatives. The present study allows us to state the correct requirements for obtaining optimal in vitro anti-T. cruzi activity. Derivatives possessing electron-withdrawing subst...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2002469
更新日期：2011-05-26 00:00:00
abstract：:A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine resid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00120a006
更新日期：1988-12-01 00:00:00
abstract：:Various 2',3'-dideoxy-L-cytidine,2',3'-dideoxy-L-uridine, and 3'-deoxy-L-thymidine analogues have been synthesized and evaluated in vitro as potential anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of 5-fluorocytosine, cytosi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00032a013
更新日期：1994-03-18 00:00:00
abstract：:The regulation of lipid metabolism and it's effect on glucose control and diabetes has received intense interest. Hormone-sensitive lipase (HSL) is a vital enzyme in lipid metabolism. A series of novel pyrrolopyrazinediones has been discovered that demonstrate submicromolar activity both in the enzyme assay and in a (...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020460y
更新日期：2003-03-27 00:00:00
abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030091l
更新日期：2003-06-19 00:00:00
abstract：:The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b00180
更新日期：2018-08-09 00:00:00
abstract：:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor proper...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00185a012
更新日期：1980-11-01 00:00:00
