Abstract：
:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Robert S,Bertolla C,Masereel B,Dogné JM,Pochet Ldoi
10.1021/jm8002697subject
Has Abstractpub_date
2008-06-12 00:00:00pages
3077-80issue
11eissn
0022-2623issn
1520-4804journal_volume
51pub_type
杂志文章abstract：:Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a039
更新日期：1986-11-01 00:00:00
abstract：:A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineopla...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000045a
更新日期：2000-07-13 00:00:00
abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00052a009
更新日期：1994-12-23 00:00:00
abstract：:2',3'-Epimino analogues of neamine, ribostamycin, and kanamycin B possessing little or no intrinsic antimicrobial activity were designed to enhance the activity of kanamycin A against bacterial strains that elaborate aminoglycoside 3'-phosphotransferases. Routes were devised for their synthesis from the parent antibio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00175a009
更新日期：1980-01-01 00:00:00
abstract：:Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characteriz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200241s
更新日期：2011-07-14 00:00:00
abstract：:Hepatitis C virus infection constitutes a serious health problem in need of more effective therapies. Nucleoside analogues with improved exposure, efficacy, and selectivity are recognized as likely key components of future HCV therapy. 2'-C-Methylguanosine triphosphate has been known as a potent inhibitor of HCV RNA p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1003792
更新日期：2010-07-08 00:00:00
abstract：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501635e
更新日期：2015-01-22 00:00:00
abstract：:Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00112a017
更新日期：1991-08-01 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：:We describe a new method, Compass, for predicting the biological activities of molecules based on the activities and three-dimensional structures of other molecules. The method improves on previous techniques by representing only the surface of molecules, by incorporating a nonlinear statistical method, and by automat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00041a010
更新日期：1994-07-22 00:00:00
abstract：:Our laboratory recently reported the development of novel prodrug chemistry for the intracellular delivery of phosphotyrosine mimetics. This chemistry has now been adapted for the synthesis of a prodrug that delivers the nonhydrolyzable difluoromethylphosphonate moiety intracellularly. Activation of the prodrug genera...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061146x
更新日期：2007-02-22 00:00:00
abstract：:A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950372w
更新日期：1996-01-05 00:00:00
abstract：:Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020044d
更新日期：2002-11-07 00:00:00
abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501792c
更新日期：2015-02-26 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：:Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101092u
更新日期：2010-12-09 00:00:00
abstract：:The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00473
更新日期：2015-06-11 00:00:00
abstract：:Six new analogues of 1α,25-dihydroxy-19-norvitamin D(3) (3a-4b, 5, and 6) were prepared by a convergent synthesis applying the Wittig-Horner reaction as a key step. The influence of methyl groups at C-22 on their biological activity was examined. It was established that both in vitro and in vivo activity is strongly d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300187x
更新日期：2012-05-10 00:00:00
abstract：:We present a novel protein-ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050540c
更新日期：2006-01-26 00:00:00
abstract：:Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic inter...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9009668
更新日期：2009-09-24 00:00:00
abstract：:A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm981012m
更新日期：1998-10-08 00:00:00
abstract：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00173a017
更新日期：1990-11-01 00:00:00
abstract：:2-Fluoro-, 4-fluoro-, and 6-fluorophenylephrine (6-FPE) were synthesized from the corresponding fluorinated 3-hydroxybenzaldehydes. New routes to 2-fluoro- and 6-fluoro-3-hydroxybenzaldehydes were developed based on regioselective lithiation of 2- and 4-[(dimethyl-tert-butylsilyl)oxy]fluorobenzene ortho to fluorine. A...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00160a030
更新日期：1986-10-01 00:00:00
abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990014j
更新日期：1999-07-15 00:00:00
abstract：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00640
更新日期：2016-09-08 00:00:00
abstract：:Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5007947
更新日期：2014-07-24 00:00:00
abstract：:The preparation, determination of isomeric configuration, and antifungal properties of (E)-1-(5-chlorothien-2-yl)-2-(1H-imidazol-1-yl)ethanone 2,6-dichlorophenylhydrazone hydrochloride (1) are described. In vitro, compound 1 has been shown to have activity against Candida albicans comparable with miconazole. When admi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00357a023
更新日期：1983-03-01 00:00:00
abstract：:A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for D2 receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9810396
更新日期：1998-12-31 00:00:00
abstract：:In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a600
更新日期：1982-01-01 00:00:00
abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm015545y
更新日期：2001-12-20 00:00:00
