Abstract:
:A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were devoid of significant activity in any of the other CNS (anticonvulsant, muscle relaxant, and depressant) assays. The most active compound in the in vivo screen for antidepressant activity (reversal of reserpine-induced hypothermia), 2-[(methoxycarbonyl)amino]-5-phenyl-1,4,5,6-tetrahydropyrimidine was considerably more potent than tricyclic antidepressant (TCA) standards. The 2-amino parent compound on the other hand was greater than 100-fold as effective as TCA's in in vitro inhibition of norepinephrine and dopamine uptake.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Weinhardt K,Wallach MB,Marx Mdoi
10.1021/jm00383a002subject
Has Abstractpub_date
1985-06-01 00:00:00pages
694-8issue
6eissn
0022-2623issn
1520-4804journal_volume
28pub_type
杂志文章abstract::Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00384a022
更新日期:1987-01-01 00:00:00
abstract::18-β-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in cancer cells. The current study aims to characterize the anticancer effects of 17 novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be the most potent...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200285z
更新日期:2011-10-13 00:00:00
abstract::The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its me...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm701093y
更新日期:2008-02-28 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::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::Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done s...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b00154
更新日期:2017-05-11 00:00:00
abstract::The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbon...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00087a018
更新日期:1992-05-01 00:00:00
abstract::High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identify...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501778s
更新日期:2015-03-12 00:00:00
abstract::CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 in...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b01077
更新日期:2018-11-08 00:00:00
abstract::A series of phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s have been synthesized and evaluated as potential hypolipidemic agents. Compound 18 (CI-924) was found to be the most potent compound in this series. In rats, compound 18 not only reduced low-density lipoprotein cholesterol but also increased high-density li...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00361a015
更新日期:1983-07-01 00:00:00
abstract::We report twelve analogues of [Pmp1,D-Trp2,Arg8]oxytocin, ANTAG (Pmp = beta, beta-pentamethylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as measured in a uterotonic assay. Nine of the following analogues were designed by replacement of ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00111a025
更新日期:1991-07-01 00:00:00
abstract::Mercaptopurine (6-MP), thioguanine (6-TG), and azathioprine (AZA) are purine antimetabolites introduced as anticancer or immunosuppressive drugs decades ago. Methylated AZA, called MAZA, is among the investigational drugs. The present study compares MAZA to the widely recognized drugs AZA, 6-MP, and 6-TG with respect ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0495273
更新日期:2005-06-30 00:00:00
abstract::Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a defin...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b00843
更新日期:2019-05-23 00:00:00
abstract::A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the co...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00046a006
更新日期:1994-09-30 00:00:00
abstract::Four novel steroidal alpha-methylene delta-lactones have been synthesized and shown to be active against human nasopharyngeal carcinoma (KB) cells in culture. The syntheses involved the use of known alpha-methylenation procedures. In addition, the lactone 6 was directly methylenated by reaction with CH2O/KOH or Et2NH/...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00175a019
更新日期:1980-01-01 00:00:00
abstract::Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm5013984
更新日期:2015-01-08 00:00:00
abstract::A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00015a012
更新日期:1995-07-21 00:00:00
abstract::A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) recep...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm001124p
更新日期:2001-06-07 00:00:00
abstract::The synthesis and biological evaluation of a series of novel 1-(aryloxy)-2-propanolamines and several related deshydroxy analogues are described. Compounds 4-29 were prepared and investigated for their class III electrophysiological activity in isolated canine Purkinje fibers and in anesthetized open-chest dogs. None ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00115a010
更新日期:1991-11-01 00:00:00
abstract::The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf splee...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00100a025
更新日期:1992-10-30 00:00:00
abstract::A total of 53 N-benzoylated phenoxazines and phenothiazines, including their S-oxidized analogues, were synthesized and evaluated for antiproliferative activity, interaction with tubulin, and cell cycle effects. Potent inhibitors of multiple cancer cell lines emerged with the 10-(4-methoxybenzoyl)-10H-phenoxazine-3-ca...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm200436t
更新日期:2011-06-23 00:00:00
abstract::The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00794
更新日期:2016-09-08 00:00:00
abstract::Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we h...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070842+
更新日期:2008-02-28 00:00:00
abstract::Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxa...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.5b00585
更新日期:2015-09-10 00:00:00
abstract::Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm061078e
更新日期:2007-04-19 00:00:00
abstract::We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm950197j
更新日期:1996-01-05 00:00:00
abstract::It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably ran...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.jmedchem.5b02008
更新日期:2016-05-12 00:00:00
abstract::Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm800621x
更新日期:2008-10-09 00:00:00
abstract::To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm501552x
更新日期:2014-12-11 00:00:00
abstract::Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase i...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00045
更新日期:2020-04-23 00:00:00