Abstract：
:The synthesis, antiarrhythmic activity, and blood hydrolysis properties of a series of mono- and bis(aminomethyl)phenylacetic acid esters related to a previously reported class Ic antiarrhythmic agent (ACC-9358) are described. Of the various oxa-, aza-, thia-, and carbacyclic esters initially prepared in the bis(pyrrolidinomethyl)-4-hydroxyphenylacetic acid series, the 1,4-benzodioxanyl-2-methyl(3q) and the thienyl-2-methyl(31) esters were evaluated in vivo for antiarrhythmic efficacy. In addition, a number of monoappended phenylacetic esters of 3q with or without the 4-hydroxy group were also prepared for evaluation of antiarrhythmic, lipophilic, and metabolic properties. Of these compounds, 3q possessed the most desirable pharmacological and pharmacokinetic profile.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Chorvat RJ,Black LA,Ranade VV,Barcelon-Yang C,Stout DM,Brown BS,Stampfli HF,Quon CYdoi
10.1021/jm00069a007subject
Has Abstractpub_date
1993-08-20 00:00:00pages
2494-8issue
17eissn
0022-2623issn
1520-4804journal_volume
36pub_type
杂志文章abstract：:The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00089a005
更新日期：1992-05-29 00:00:00
abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970156i
更新日期：1997-10-10 00:00:00
abstract：:Treatment of a protected 9-(5, 6-dideoxy-beta-D-ribo-hex-5-ynofuranosyl)adenine derivative with silver nitrate and N-iodosuccinimide (NIS) and deprotection gave the 6'-iodo acetylenic nucleoside analogue 3c. Halogenation of 3-O-benzoyl-5,6-dideoxy-1, 2-O-isopropylidene-alpha-D-ribo-hex-5-enofuranose gave 6-halo acetyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980163m
更新日期：1998-09-24 00:00:00
abstract：:Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01951
更新日期：2019-04-11 00:00:00
abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00107a045
更新日期：1991-03-01 00:00:00
abstract：:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00527
更新日期：2017-05-25 00:00:00
abstract：:A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-brom...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00122a019
更新日期：1989-02-01 00:00:00
abstract：:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00135a003
更新日期：1981-03-01 00:00:00
abstract：:In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4001242
更新日期：2013-07-11 00:00:00
abstract：:New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00064a001
更新日期：1993-06-11 00:00:00
abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00078
更新日期：2016-05-12 00:00:00
abstract：:A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960662s
更新日期：1997-09-26 00:00:00
abstract：:In order to find a new class of anti-Helicobacter pylori (H. pylori) agents, a series of 4-[(3-acetamido)phenyl]-2-(substituted guanidino)thiazoles and some structurally rigid analoges were synthesized and evaluated for antimicrobial activity against H. pylori. Among the compounds obtained, high anti-H. pyrori activit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000169n
更新日期：2000-08-24 00:00:00
abstract：:A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00100a007
更新日期：1992-10-30 00:00:00
abstract：:A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antim...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00173a028
更新日期：1990-11-01 00:00:00
abstract：:Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b02022
更新日期：2020-03-26 00:00:00
abstract：:New beta-adrenergic blocking agents, most of which do not contain an aromatic nucleus, were synthesized. They were derived either from alkylamino-aliphatic oxime ethers or alkylamino-aliphatic ethers. Most active among these are O-[3-(tert-butylamino)-2-hydroxypropyl]acetoxime (8; trachea pA2 = 7.65) and 1-isobutoxy-3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00180a007
更新日期：1980-06-01 00:00:00
abstract：:Metoclopramide (1) is a gastric motility stimulant and a weak dopamine and 5-HT3 receptor antagonist. Conformational restriction of the (diethylamino)ethyl side chain of 1 in the form of the azabicyclic tropane gave 3, a very potent gastric motility stimulant and 5-HT3 receptor antagonist but devoid of significant dop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00169a016
更新日期：1990-07-01 00:00:00
abstract：:A series of novel compounds having a benzothiazoline skeleton was studied for their structure-activity relationship (SAR) with respect to Ca2+ antagonistic activity. As test compounds, analogues of 3-acyl-2-arylbenzothiazolines (3) were synthesized. Benzothiazoline derivatives (3) exerted higher Ca2+ antagonistic acti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00400a006
更新日期：1988-05-01 00:00:00
abstract：:A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00109a005
更新日期：1991-05-01 00:00:00
abstract：:A novel series of aryl 1-but-3-ynyl-4-phenyl-1,2,3,6-tetrahydropyridines with dopaminergic activity is described. The structure-activity relationships of this series were studied by synthesis of analogs and evaluation of their affinities for the dopamine (DA) D2 receptor and inhibition of locomotor activity (LMA) in r...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950721m
更新日期：1996-08-02 00:00:00
abstract：:Self-organizing maps were trained to separate high- and low-active propafenone-type inhibitors of P-glycoprotein. The trained maps were subsequently used to identify highly active compounds in a virtual screen of the SPECS compound library. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060604z
更新日期：2007-04-05 00:00:00
abstract：:Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to the discovery of structurally diverse TopoI inhibitors. From 23 compounds selected by virtual screening, a total of 14 compounds were found to be TopoI in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100387d
更新日期：2010-11-11 00:00:00
abstract：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00154a017
更新日期：1986-04-01 00:00:00
abstract：:Enantiostructure-activity studies of chlorophenoxybutyric and propionic acids have provided evidence for the dissociation of serum cholesterol lowering and platelet antiaggregatory activities from the adverse chloride ion channel mediated myotonic effects of these compounds. R-(+) propionic and butyric acid enantiomer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00391a001
更新日期：1987-08-01 00:00:00
abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01750
更新日期：2019-03-28 00:00:00
abstract：:On the basis of our previous observation that N1-alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. N1-Allyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00050a018
更新日期：1994-11-25 00:00:00
abstract：:A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00224a020
更新日期：1976-02-01 00:00:00
abstract：:A series of 10-ketomorphinan analogues were synthesized, and their binding affinity at all three opioid receptors was investigated. In most cases, high affinity at micro and kappa receptors, and lower affinity at delta receptor was observed, resulting in good selectivity for micro and kappa receptors. A wide range of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304156
更新日期：2004-01-01 00:00:00
abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010037+
更新日期：2001-06-21 00:00:00
