Abstract：
:It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3 beta-(3,4- dichlorophenyl)tropane-2 beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Meltzer PC,Liang AY,Brownell AL,Elmaleh DR,Madras BKdoi
10.1021/jm00059a010subject
Has Abstractpub_date
1993-04-02 00:00:00pages
855-62issue
7eissn
0022-2623issn
1520-4804journal_volume
36pub_type
杂志文章abstract：:Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00235a002
更新日期：1975-01-01 00:00:00
abstract：:The cardiac activity of a series of analogues of the positive inotropic bipyridines amrinone (5-amino-[3,4'-bipyridin]-6(1H)-one) and milrinone (2-methyl-5-cyano-[3,4'-bipyridin]-6(1H)-one) was evaluated in vitro in a rabbit myocardial membrane Mg(2+)-dependent, Ca(2+)-stimulable adenosine triphosphatase (Ca(2+)-ATPas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00011a018
更新日期：1995-05-26 00:00:00
abstract：:In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C N...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058003f
更新日期：2005-06-30 00:00:00
abstract：:A series of conjugated hyaluronic acid particles (HAP), composed of a hydrophobic anticancer drug core and hydrophilic cyclodextrin/hyaluronic acid shell, were prepared through self-assembling and characterized by (1)H NMR titration, electron microscopy, zeta potential, and dynamic light-scattering experiments. The na...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4014168
更新日期：2013-12-12 00:00:00
abstract：:Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.5b00361
更新日期：2016-01-28 00:00:00
abstract：:A series of 9-hydrazono-4H-pyrido[1,2-a]pyrimidin-4-ones was prepared. The compounds were evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. Structure-activity relationship studies revealed that the presence of a monosubstituted hydrazone moiety in position 9 and an unsubstituted 2-posi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00362a008
更新日期：1983-08-01 00:00:00
abstract：:The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a023
更新日期：1995-07-07 00:00:00
abstract：:Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00358a021
更新日期：1983-04-01 00:00:00
abstract：:The triphosphates of antiviral 2',3'-dideoxynucleosides (ddNs) are the active chemical species that inhibit viral DNA synthesis. The inhibition involves incorporation of ddNMP into DNA and subsequent chain termination. A conceivable strategy for antiviral drugs is to employ nucleoside 5'-triphosphate mimics that can e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040101y
更新日期：2005-04-07 00:00:00
abstract：:An application of the neural network to quantitative structure-activity relationship (QSAR) analysis has been studied. The new method was compared with the linear multiregression analysis in various ways. It was found that the neural network can be a potential tool in the routine work of QSAR analysis. The mathematica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm00171a037
更新日期：1990-09-01 00:00:00
abstract：:The antiproliferative activity of the 14 isomeric monoxylosylated dihydroxynaphthalenes has been tested in vitro toward normal HFL-1 and 3T3 A31 cells as well as transformed T24 and 3T3 SV40 cells. The antiproliferative effect toward HFL-1 cells was correlated with the polarity of the compounds. However, in the case o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0512488
更新日期：2006-03-23 00:00:00
abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00942
更新日期：2019-10-10 00:00:00
abstract：:The influence of structure on DT-diaphorase substrate activity, topoisomerase II inhibition activity, and DNA reductive alkylation was studied for the 6-aziridinylpyrrolo[1,2-alpha]benzimidazolequinones (PBIs) and the 6-acetamidopyrrolo[1,2-alpha]benzimidazolequinones (APBIs). The PBIs are reductively activated by DT-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960546p
更新日期：1997-04-25 00:00:00
abstract：:Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical appr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01683
更新日期：2021-01-31 00:00:00
abstract：:The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm400132d
更新日期：2013-09-26 00:00:00
abstract：:The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a fut...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070410z
更新日期：2007-08-09 00:00:00
abstract：:The preparation and testing of the two racemic diastereoisomers and the four optically active enantiomers of the title compound in in vitro and in vivo models for determining potential antipsychotic activity are described. Both racemic diastereoisomers and two of the four chiral enantiomers are potent and long-acting ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a025
更新日期：1980-08-01 00:00:00
abstract：:In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00447
更新日期：2018-06-28 00:00:00
abstract：:Anaplastic lymphoma kinase (ALK) is a valid target for anticancer therapy; however, potent ALK inhibitors suitable for clinical use are lacking. Because the majority of described kinase inhibitors bind in the ATP pocket of the kinase domain, we have characterized this pocket in ALK using site-directed mutagenesis, inh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060380k
更新日期：2006-09-21 00:00:00
abstract：:The specificity of nucleic acids' binders is crucial for developing this kind of drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivative...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00016
更新日期：2017-07-13 00:00:00
abstract：:Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3014635
更新日期：2013-02-28 00:00:00
abstract：:The inhibitory activity of 1058 inhibitors of the title enzymes has been formulated in 13 equations correlating chemical structure with inhibitory potency. Two types of regions in enzymes have been defined by means of pi and molar refractivity constants. The use of indicator variables has been extensively developed to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00223a015
更新日期：1976-01-01 00:00:00
abstract：:Coumarins constitute a general and totally new class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), binding at the entrance of the active site cavity. We report here that the coumarin-binding site in CAs may interact with diverse compounds, such as the antiepileptic drug lacosamide, which inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901524f
更新日期：2010-01-28 00:00:00
abstract：:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00087
更新日期：2016-04-28 00:00:00
abstract：:A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200039m
更新日期：2011-04-14 00:00:00
abstract：:A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1-9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010568y
更新日期：2002-05-23 00:00:00
abstract：:In a continuation of studies directed toward characterizing the hydrophilic pocket within the aromatic ring binding region of the active site of phenylethanolamine N-methyltransferase (PNMT), 5-, 6-, 7-, and 8-hydroxy-1,2,3,4-tetrahydroisoquinoline were prepared and evaluated as substrates and inhibitors of PNMT. In o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00395a006
更新日期：1987-12-01 00:00:00
abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00212a003
更新日期：1977-02-01 00:00:00
abstract：:The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclot...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00210a011
更新日期：1978-12-01 00:00:00
abstract：:A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives was synthesized and evaluated as inhibitors of cAMP hydrolysis by a crude human platelet phosphodiesterase preparation and as inhibitors of ADP- and collagen-induced aggregation of rabbit blood platelets. The parent structure 7a, demonstrated potent i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00113a033
更新日期：1991-09-01 00:00:00
