Abstract：
:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,9 alpha-diethyl-2'-hydroxybenzomorphan was prepared and evaluated for analgesic activity. In vitro activities were found to vary greatly, depending on the nature of the amino acid used. The N-arginyl derivative was found to be equipotent to (-)-5,9 alpha-diethyl-2'hydroxybenzomorphan and also to methionine-enkephaline in the naloxone binding assay.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt ELdoi
10.1021/jm00143a007subject
Has Abstractpub_date
1981-11-01 00:00:00pages
1297-9issue
11eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01858
更新日期：2018-02-22 00:00:00
abstract：:New imidazo[1,2-a]pyridines substituted at the 3-position have been synthesized as potential antisecretory and cytoprotective antiulcer agents. The synthetic routes began with cyclization of aminopyridines 5a,b and chloro ketones 6a,b to give imidazo[1,2-a]pyridines 7-9. The side chain at the 3-position was elaborated...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00129a028
更新日期：1989-09-01 00:00:00
abstract：:There is an urgent unmet medical need for novel antibiotics that are effective against a broad range of bacterial species, especially multidrug resistant ones. Tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent activity against Gram-positive pathogens ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01831
更新日期：2017-05-11 00:00:00
abstract：:Radiocopper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), Cu[PTSM], is under investigation as a radiopharmaceutical for evaluation of regional blood flow in the brain, heart, and kidneys because it affords relatively high levels of radioactivity in these organs upon intravenous injection, followed...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00168a035
更新日期：1990-06-01 00:00:00
abstract：:(R,S)-2-Amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid ((R,S)-APPA) is the only partial agonist at the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors so far described. In light of the pharmacological interest in partial agonists, we have now a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00033a003
更新日期：1994-04-01 00:00:00
abstract：:The glucocorticoid receptor (GR) has been linked to therapy resistance across a wide range of cancer types. Preclinical data suggest that antagonists of this nuclear receptor may enhance the activity of anticancer therapy. The first-generation GR antagonist mifepristone is currently undergoing clinical evaluation in v...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00743
更新日期：2018-09-13 00:00:00
abstract：:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00208a004
更新日期：1978-10-01 00:00:00
abstract：:Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzym...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030191r
更新日期：2003-10-09 00:00:00
abstract：:Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9811007
更新日期：1999-03-25 00:00:00
abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401328u
更新日期：2013-12-27 00:00:00
abstract：:6-Chloropurine derivatives of gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 3a, gamma-(Z)-ethylidene-2-methoxy-3-(4-nitro)benzyloxybutenolide 3b, gamma-(Z)-ethylidene-2-(4-nitro)benzyloxy-3-methoxybutenolide 3c, gamma-(Z)-ethylidene-2,3-di(4-nitro)benzyloxybutenolide 3d, and dimethylphosphono-gamma-(Z)-ethylidene-2,3-d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0004446
更新日期：2001-05-24 00:00:00
abstract：:Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500544p
更新日期：2014-07-24 00:00:00
abstract：:The adenovirus serotype Ad37 binds to and infects human corneal epithelial (HCE) cells through attachment to cellular glycoproteins carrying terminal sialic acids. By use of the crystallographic structure of the sialic acid-interacting domain of the Ad37 fiber protein in complex with sialyllactose, a set of N-acyl mod...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801609s
更新日期：2009-06-25 00:00:00
abstract：:3',4'-Dihydroxynomifensine, 8-amino-1,2,3,4-tetrahydro-4-(3,4-dihydroxyphenyl)-2-methylisoquinoli ne (1a), is an agonist of dopamine receptors in central and peripheral systems. Since this dopamine receptor agonist bears an asymmetric center at position 4, its synthesis and resolution were undertaken as part of a stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00367a006
更新日期：1984-01-01 00:00:00
abstract：:The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9910369
更新日期：1999-08-12 00:00:00
abstract：:In the treatment of cardiovascular diseases, it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin II formation, ensured by endothelial angiotensin-converting enzyme (ACE), with the diuretic and natriuretic responses due to the protection of the endogenou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00034a005
更新日期：1994-04-15 00:00:00
abstract：:KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and increasingly recognized as a target for diseases involving oxidative stress. Pharmacological intervention has focused on molecules that decrease NRF2-ubiquitination through covalent modification of KEAP1 cysteine residues, but such electrophi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00228
更新日期：2016-04-28 00:00:00
abstract：:The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01523
更新日期：2019-02-14 00:00:00
abstract：:We have synthesized several 7alpha-fluoro (F) and 7alpha-iodo (I) analogues of 5alpha-dihydrotestosterone (5alpha-DHT) and 19-nor-5alpha-dihydrotestosterone (5alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in an in vitro assay with cells that have been engineered to ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990064o
更新日期：1999-06-03 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：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00972
更新日期：2019-09-26 00:00:00
abstract：:The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a v...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01372
更新日期：2017-12-28 00:00:00
abstract：:On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300041e
更新日期：2012-05-10 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：:This article highlights our work toward the identification of a potent, selective, and efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1), led to the identification of compound 7f as a highly potent AMCase i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01051
更新日期：2018-02-08 00:00:00
abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00124a007
更新日期：1989-04-01 00:00:00
abstract：:Chemically diverse oxysterols were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against seven cancer (HT-29, HepG2, A549, PC3, LAMA-84, MCF-7, and SH-SY5Y) and two noncancerous cell lines (ARPE-19 and BJ). The influence of the oxidation pattern on rings A an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200803d
更新日期：2011-09-22 00:00:00
abstract：:Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800791f
更新日期：2009-02-26 00:00:00
abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0494873
更新日期：2004-12-02 00:00:00
abstract：:Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00038a020
更新日期：1994-06-10 00:00:00
