Abstract:
:The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Smith LH,Tucker Hdoi
10.1021/jm00222a022subject
Has Abstractpub_date
1977-12-01 00:00:00pages
1653-6issue
12eissn
0022-2623issn
1520-4804journal_volume
20pub_type
杂志文章abstract::Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional aff...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.7b01626
更新日期:2018-02-08 00:00:00
abstract::As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00134a021
更新日期:1981-02-01 00:00:00
abstract::C-terminally truncated fragments of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) were tested for their ability to stimulate amylase secretion from pancreatic acinar cells and relax precontracted mesenteric arteries. h-alpha-CGRP, h-alpha-CGRP (1-36), h-alpha-CGRP (1-35), and h-alpha-CGRP (1-34) were made...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00069a012
更新日期:1993-08-20 00:00:00
abstract::Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Additionally, the high ...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.0c00936
更新日期:2020-09-10 00:00:00
abstract::Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0614230
更新日期:2007-03-22 00:00:00
abstract::We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm900611t
更新日期:2009-08-27 00:00:00
abstract::A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00181a003
更新日期:1980-07-01 00:00:00
abstract::Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm301824k
更新日期:2013-04-25 00:00:00
abstract::The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00390a021
更新日期:1987-07-01 00:00:00
abstract::Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b00087
更新日期:2016-04-28 00:00:00
abstract::Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00228a014
更新日期:1976-06-01 00:00:00
abstract::A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and associatio...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm070784s
更新日期:2007-11-29 00:00:00
abstract::In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00142a002
更新日期:1981-10-01 00:00:00
abstract::The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.6b01234
更新日期:2016-11-23 00:00:00
abstract::The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature me...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00229a015
更新日期:1976-07-01 00:00:00
abstract::Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure-activity relationships of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this study to the pur...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm970233+
更新日期:1997-08-15 00:00:00
abstract::Structure dependent efficacy studies in the field of selective D4 ligands led to the 2-aminomethyl substituted azaindole 2 (FAUC 213) that displayed strong D4 binding, high subtype selectivity, and complete antagonist properties in ligand-induced mitogenesis experiments. According to our schematic molecular model, the...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm015522j
更新日期:2001-08-16 00:00:00
abstract::The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0496133
更新日期:2004-09-23 00:00:00
abstract::An extension of the Mannich reaction, in which aminomethylation of the five position of uracil, is reported. Thus, primary and secondary alkylamines and primary aromatic amines containing ring-activating groups led to the title compounds 3-10. Compound 11 in which the aromatic ring contains the ring-deactivating nitro...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00224a032
更新日期:1976-02-01 00:00:00
abstract::Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (P...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm101540e
更新日期:2011-04-14 00:00:00
abstract::A novel method for quantitative structure-activity relationship (QSAR) analysis is presented. The method, which does not assume any particular functional form for the QSAR, develops nonlinear relationships between parameters describing a set of molecules and the activity of the molecules. For the QSAR of the inhibitio...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960197z
更新日期:1996-08-30 00:00:00
abstract::Target identification is a high-priority, albeit challenging, aspect of drug discovery. Diazirine-based photoaffinity probes (PAPs) can facilitate the process by covalently capturing transient molecular interactions. This can help identify target proteins and map the ligand's interactome. Diazirine probes have even be...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1021/acs.jmedchem.7b01561
更新日期:2018-08-23 00:00:00
abstract::The dihydrochalcone derivatives of the bitter flavonoids naringin and neohesperedin are intensely sweet. Phyllodulcin is as sweet as the dihydrochalcones with similar taste properties although its structure apparently resembles that of bitter flavanone or flavone. Multifaceted approaches, including X-ray crystal struc...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00021a022
更新日期:1995-10-13 00:00:00
abstract::Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm4015313
更新日期:2014-02-27 00:00:00
abstract::A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydr...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00144a013
更新日期:1981-12-01 00:00:00
abstract::Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto th...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm300509y
更新日期:2012-08-23 00:00:00
abstract::A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta I, be...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm960581w
更新日期:1996-12-20 00:00:00
abstract::We have designed and synthesized 16 new olean- and urs-1-en-3-one triterpenoids with various modified rings C as potential antiinflammatory and cancer chemopreventive agents and evaluated their inhibitory activities against production of nitric oxide induced by interferon-gamma in mouse macrophages. This investigation...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm0002230
更新日期:2000-11-02 00:00:00
abstract::Chemical investigations leading to the construction of bis(bioreductive) alkylating agents having both conformationally restricted and mobile spacer regions are described. Two targets having the conformationally mobile ethylene spacer group, namely, 2,2'-ethylenebis[6-(hydroxymethyl)-p-benzoquinone] diacetate (3b) and...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/jm00366a004
更新日期:1983-12-01 00:00:00
abstract::The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to d...
journal_title:Journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1021/acs.jmedchem.8b01433
更新日期:2018-11-21 00:00:00