Abstract：
:In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release of histamine in rat passive peritoneal anaphylaxis (PPA). The most potent compound, 1-[2-hydroxy-3-[(4-hydroxy-3-nitrocoumarin-7-yl)oxy]propyl]-4- (4-chlorobenzyl)piperazine, 30, had a pA2 of 9.0 against histamine on guinea pig ileum and inhibited histamine release in the rat PPA test with a potency similar to that of disodium cromoglycate.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Buckle DR,Outred DJ,Smith H,Spicer BAdoi
10.1021/jm00377a013subject
Has Abstractpub_date
1984-11-01 00:00:00pages
1452-7issue
11eissn
0022-2623issn
1520-4804journal_volume
27pub_type
杂志文章abstract：:A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, following the discovery of activity for prototype thioindole 2. Structure-activity relationships were explored, leading to many potent antitachycardiac agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00356a021
更新日期：1983-02-01 00:00:00
abstract：:The natural abundance 13C magnetic resonance spectra of a series of sulfonamide drugs(sulfanilamide, sulfaguanidine,sulfathiazole, sulfasuxidine, sulfadiazine, sulfamerazine, sulfamethiazine, and sulfapyridine) have been determined at 25.15 MHz employing the pulse Fourier transform technique. The chemical shefts have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00239a014
更新日期：1975-05-01 00:00:00
abstract：:A series of 3-(4-phenoxyphenyl)-1H-pyrazoles were synthesized and characterized as potent state-dependent sodium channel blockers. A limited SAR study was carried out to delineate the chemical requirements for potency. The results indicate that the distal phenyl group is critical for activity but will tolerate lipophi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030498q
更新日期：2004-03-11 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 efficacious dose of a drug is perhaps the most holistic metric reflecting its therapeutic potential. Dose is predicted at many stages in drug discovery and development. Prior to the 1990s, dose prediction was limited to the drug "working" at a reasonable dose and dose regimen in an animal model. Through the early ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01365
更新日期：2020-06-25 00:00:00
abstract：:Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing al...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800993r
更新日期：2008-12-25 00:00:00
abstract：:The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4009345
更新日期：2013-12-27 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：:Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention toward that go...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00898
更新日期：2020-03-12 00:00:00
abstract：:Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an ant...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00178a020
更新日期：1980-04-01 00:00:00
abstract：:Hydrolysis of the carbamate side chains in phenserine [(-)1] and physostigmine [(-)2] yields the metabolite (-)-eseroline (3), and the red dye rubreserine (4) on air oxidation of the former compound. Both compounds lacked anticholinesterase activity in concentrations up to 30 mM, which would be unachievable in vivo. A...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9800494
更新日期：1998-06-18 00:00:00
abstract：:Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tubercu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00432
更新日期：2016-06-23 00:00:00
abstract：:We have discovered N-butyl-N'-[2-(dimethylamino)-6-[3-(4-phenyl-1H- imidazol-1-yl)propoxy]phenyl]urea (4), a novel, potent, and systemically bioavailable inhibitor of ACAT (acylCoA:cholesterol O-acyltransferase). The structure-activity relationships (SARs) of this lead compound 4 were investigated by systematic modifi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00063a013
更新日期：1993-05-28 00:00:00
abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a020
更新日期：1985-02-01 00:00:00
abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00134
更新日期：2016-04-28 00:00:00
abstract：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00371a005
更新日期：1984-05-01 00:00:00
abstract：:Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and methy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049469l
更新日期：2005-06-16 00:00:00
abstract：:1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a009
更新日期：1985-10-01 00:00:00
abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00229a010
更新日期：1976-07-01 00:00:00
abstract：:The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4+ cell types from bone marrow to peripheral circulation. We have discovered a novel series of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01322
更新日期：2018-02-08 00:00:00
abstract：:We disclose the first selective, nonpeptidic, small-molecule somatostatin receptor subtype 5 (SST5R) antagonists that were identified by a chemogenomics approach based on the analysis of the homology of amino acids defining the putative consensus drug binding site of SST5R. With this strategy, opioid, histamine, dopam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701143p
更新日期：2007-12-13 00:00:00
abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030792i
更新日期：2003-08-14 00:00:00
abstract：:Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent γ-ca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00958
更新日期：2015-08-27 00:00:00
abstract：:Photodynamic therapy uses a combination of light, oxygen, and a photosensitizer to induce the death of malignant cells. To improve the selectivity of a photosensitizer toward cancerous cells that express gonadotropin-releasing hormone (GnRH) receptors, protoporphyrin IX (PpIX) was conjugated to a GnRH agonist, [d-Lys6...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020535y
更新日期：2003-09-11 00:00:00
abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm401937a
更新日期：2014-10-23 00:00:00
abstract：:A number of cytostatic compounds (2-4, 7, and 8), which can be described as "diaryl", inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubulin. They differ, however, in the separation of the two aryl moieties. To attempt to understand t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00084a011
更新日期：1992-03-20 00:00:00
abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01112
更新日期：2018-09-13 00:00:00
abstract：:The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990159q
更新日期：1999-09-23 00:00:00
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 de...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00383a002
更新日期：1985-06-01 00:00:00
abstract：:Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in ac...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00809
更新日期：2019-08-08 00:00:00
