Abstract：
:The need for drugs that lack the obtrusive and limiting side effects of the tricyclic antidepressants has prompted the search for agents with greatly enhanced selectivity for specific mechanisms believed to be essential for antidepressant efficacy. The potential role of derangements of 5-HT pathways in the etiology of depression has long been suspected and has given impetus to the development of newer compounds that accentuate inhibition of serotonin reuptake. This paper presents structure-activity relationships for a series of cis-1-amino-4-(substituted-aryl)tetralins, which are surprisingly potent and selective inhibitors of serotonin uptake in in vitro models. These compounds are pharmacologically distinct from corresponding members of the trans series, which also potently block uptake of dopamine and norepinephrine. The activity in both cis and trans series is stereospecific, being restricted to the cis-(1S,4S) and the trans-(1R,4S) enantiomers.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Welch WM,Kraska AR,Sarges R,Koe BKdoi
10.1021/jm00377a021subject
Has Abstractpub_date
1984-11-01 00:00:00pages
1508-15issue
11eissn
0022-2623issn
1520-4804journal_volume
27pub_type
杂志文章abstract：:HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00994
更新日期：2016-12-22 00:00:00
abstract：:In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) models are important tools in combating late-stage attrition in the drug discovery process. This work shows how ADMET models can be combined to tailor predictions depending on one's needs. We demonstrate how the judicious use of data and c...
journal_title：Journal of medicinal chemistry
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更新日期：2005-02-24 00:00:00
abstract：:A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00206a006
更新日期：1978-08-01 00:00:00
abstract：:In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-D...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00101a003
更新日期：1992-11-13 00:00:00
abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970159v
更新日期：1998-08-13 00:00:00
abstract：:The enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) catalyzes the final step in the biosynthesis of epinephrine and is a potential drug target, primarily for the control of hypertension. Unfortunately, many potent PNMT inhibitors also possess significant affinity for the a2-adrenoceptor, which compli...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01475
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abstract：:Chemical probes are small molecules designed to bind to a specific protein and disrupt the proteins function. Although many inhibitors are reported for human carbonic anhydrase (CA) enzymes, few may be considered useful as chemical probes as they exhibit broad action against the 12 catalytically active CA isozymes. In...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01228
更新日期：2015-09-24 00:00:00
abstract：:Peptidoaminobenzophenones (1), terminal N-substituted peptidoaminobenzophenones (14), and acylglycylaminobenzophenones (16) were prepared as a novel series of ring-opened derivatives of 1,4-benzodiazepine. Z-Gly- and Z-Ala-N-methylaminobenzophenones (4) were treated with HBr-HOAc to give Gly- and Ala-N-methylaminobenz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00133a006
更新日期：1981-01-01 00:00:00
abstract：:Primaquine (I) has been extensively used in combination with other drugs in the radical cure of relapsing malaria as well as for prophylaxis or the interruption of transmission. This, coupled with the activity data reported for 4-methylprimaquine (II), has led to the synthesis of a series of 14 4-substituted analogues...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00219a003
更新日期：1977-09-01 00:00:00
abstract：:Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01989
更新日期：2020-08-27 00:00:00
abstract：:In this paper, a peptide substrate (Pep8) of TSSK1 is identified. Using Pep8 as a substrate, two homogeneous and efficient assays for TSSK1 inhibitors screening have been developed, including luminescent kinase assay and LC-MS-based high-throughput assay. Two classes of compounds were identified that are able to effic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9002846
更新日期：2009-07-23 00:00:00
abstract：:A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00166a010
更新日期：1990-04-01 00:00:00
abstract：:A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5008648
更新日期：2014-08-28 00:00:00
abstract：:Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4011466
更新日期：2013-10-10 00:00:00
abstract：:The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01666
更新日期：2018-05-24 00:00:00
abstract：:Potential E- and P-selectin inhibitors were synthesized to explore a hydrophobic area on the E-selectin surface and the PSGL-1 protein binding site on the P-selectin surface that was recently defined by crystallography. Three series of mannose-based compounds (libraries A, B, and C) were synthesized using solution pha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010390f
更新日期：2002-04-11 00:00:00
abstract：:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00156a006
更新日期：1986-06-01 00:00:00
abstract：:Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970872k
更新日期：1998-12-17 00:00:00
abstract：:Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：1994-06-10 00:00:00
abstract：:An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：1991-08-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a013
更新日期：1985-10-01 00:00:00
abstract：:A series of N-alkyl-3-[m-(trifluoromethyl)phenyl]-5-hydroxy-2-pyrrolidinones and N-alkyl-3-(trifluoromethyl)-cinnamamides were prepared and screened in a series of tests designed to detect potential sleep inducers. The more active members of the series were evaluated for their ability to induce sleep in Cebus monkeys....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00379a007
更新日期：1985-01-01 00:00:00
abstract：:(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm034073f
更新日期：2003-07-17 00:00:00
abstract：:Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8...
journal_title：Journal of medicinal chemistry
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更新日期：2000-06-01 00:00:00
abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00197
更新日期：2017-07-13 00:00:00
abstract：:Aberrant activation of S6 kinase 1 (S6K1) is found in many diseases, including diabetes, aging, and cancer. We developed ATP competitive organometallic kinase inhibitors, EM5 and FL772, which are inspired by the structure of the pan-kinase inhibitor staurosporine, to specifically inhibit S6K1 using a strategy previous...
journal_title：Journal of medicinal chemistry
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更新日期：2015-01-08 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4017976
更新日期：2014-02-27 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00370a006
更新日期：1984-04-01 00:00:00
abstract：:On the basis of docking studies carried out using the recently published cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, whic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0603466
更新日期：2006-10-05 00:00:00
abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00165a029
更新日期：1990-03-01 00:00:00
