Abstract：
:Certain phenylalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors. It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identified population of serotonin 5-HT1C receptors. The purpose of the present investigation was to determine whether simple phenylalkylamines bind selectively at one population of receptors over the other. An examination of 34 derivatives reveals (i) similar structure-affinity relationships and (ii) a significant correlation (r = greater than 0.9, n = 25) between 5-HT1C and 5-HT2 affinity. None of the compounds included in the present study displayed more than a 10-fold selectivity for one population of these receptors over the other; the results suggest that these compounds (including the widely used 5-HT2 agonists DOB and DOI) are 5-HT1C/5-HT2 agents.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Glennon RA,Raghupathi R,Bartyzel P,Teitler M,Leonhardt Sdoi
10.1021/jm00082a014keywords:
subject
Has Abstractpub_date
1992-02-21 00:00:00pages
734-40issue
4eissn
0022-2623issn
1520-4804journal_volume
35pub_type
杂志文章abstract：:A series of 1-(4-fluorophenyl)-1H-indoles substituted at the 3-position with 1-piperazinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperidinyl was synthesized. Within all three subseries potent dopamine D-2 and serotonin 5-HT2 receptor affinity was found in ligand binding studies. Quipazine-induced head twitches in rat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00084a014
更新日期：1992-03-20 00:00:00
abstract：:A novel synthetic route to the cyclostellettamines 1 using as the key step a microwave-mediated macrocyclic ring-closing metathesis of precursors bispyridinium dienes 10 followed by catalytic hydrogenation has been developed. The open-chain bispyridinium dienes 10 showed uniformly higher histone deacetylase (HDAC) inh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070028m
更新日期：2007-05-17 00:00:00
abstract：:The binding affinities of a selected series of Gd(III) chelates bearing bile acid residues, potential hepatospecific MRI contrast agents, to a liver cytosolic bile acid transporter, have been determined through relaxivity measurements. The Ln(III) complexes of compound 1 were selected for further NMR structural analys...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070397i
更新日期：2007-11-01 00:00:00
abstract：:We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II'...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970262k
更新日期：1997-10-24 00:00:00
abstract：:Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped ve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0108754
更新日期：2001-10-25 00:00:00
abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00855
更新日期：2020-08-27 00:00:00
abstract：:Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this l...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5013352
更新日期：2015-01-08 00:00:00
abstract：:A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000145g
更新日期：2001-05-10 00:00:00
abstract：:We report novel inhibitors of Gli1-mediated transcription as potential anticancer agents. Focused chemical libraries were designed and assessed for inhibition of functional cell-based Gli1-mediated transcription and selective toxicity toward cancer cells. The SAR was revealed, and the selectivity of the lead compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900106f
更新日期：2009-07-23 00:00:00
abstract：:Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a functional assay, resulting in the identification of an isothiourea h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901472u
更新日期：2010-02-11 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：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00051a016
更新日期：1994-12-09 00:00:00
abstract：:Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. H...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020536q
更新日期：2003-04-10 00:00:00
abstract：:The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (σ1R) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in σ-1 and σ-2 receptor binding assays. The nature of the pyrimidine scaffold ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501207r
更新日期：2014-12-26 00:00:00
abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061031t
更新日期：2006-12-28 00:00:00
abstract：:Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)-4-oxobutyl]piperazine), a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950894b
更新日期：1996-07-19 00:00:00
abstract：:Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformati...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00053a001
更新日期：1993-01-08 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
pub_type： 杂志文章
doi：10.1021/jm991140q
更新日期：2000-06-01 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：:Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060216x
更新日期：2006-09-07 00:00:00
abstract：:The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8009102
更新日期：2009-01-22 00:00:00
abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00191a005
更新日期：1979-05-01 00:00:00
abstract：:A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. Th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00057a010
更新日期：1993-03-05 00:00:00
abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060351+
更新日期：2006-08-24 00:00:00
abstract：:The mitotic spindle is a validated target for cancer chemotherapy. Drugs such as taxanes and vinca alkaloids specifically target microtubules and cause the mitotic spindle to collapse. However, toxicity and resistance are problems associated with these drugs. Thus, alternative approaches to inhibiting the mitotic spin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100991m
更新日期：2011-03-24 00:00:00
abstract：:We have found that (R,S)-1-(phenylthio)-aminopropane (4a), a synthetic alternate substrate for the terminal enzyme of norepinephrine biosynthesis, dopamine beta-monooxygenase (DBM), is both an indirect sympathomimetic and a potent antihypertensive agent in spontaneously hypertensive rats. We demonstrate herein that th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00107a031
更新日期：1991-03-01 00:00:00
abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00533
更新日期：2017-06-08 00:00:00
abstract：:A series of analogues of Pro-Leu-Gly-NH2 (PLG) in which the leucine residue has been replaced with the aliphatic amino acids L-isoleucine, L-2-aminohexanoic acid (Ahx), L-2-aminopentanoic acid, and L-2-aminobutanoic acid and the aromatic amino acids L-phenylalanine, L-phenylglycine, L- and D-2-amino-4-phenylbutanoic a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00168a045
更新日期：1990-06-01 00:00:00
abstract：:The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the va...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.6b01575
更新日期：2017-07-13 00:00:00
abstract：:Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0340703
更新日期：2003-06-05 00:00:00
