Abstract：
:Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Crider AM,Kolczynski TM,Yates KMdoi
10.1021/jm00177a024subject
Has Abstractpub_date
1980-03-01 00:00:00pages
324-6issue
3eissn
0022-2623issn
1520-4804journal_volume
23pub_type
杂志文章abstract：:Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00226a002
更新日期：1976-04-01 00:00:00
abstract：:A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of the novel amidinoindole and benzofuran compounds, I and II. Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 29, which displayed an IC50 value o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704863
更新日期：1997-12-19 00:00:00
abstract：:Lead generation for difficult-to-drug targets that have large, featureless, and highly lipophilic or highly polar and/or flexible binding sites is highly challenging. Here, we describe how cores of macrocyclic natural products can serve as a high-quality in silico screening library that provides leads for difficult-to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01569
更新日期：2021-01-28 00:00:00
abstract：:2-Acetamido-5-O-acetyl-6-O-acyl-2-deoxy-3-O-[(R)-2-propionyl-L-alanyl-D- isoglutamine]-D-glucofuranoses, designed as prodrug forms of the corresponding immunoadjuvant-active 6-O-acyl derivatives of N-acetylmuramyl dipeptide (MDP), were synthesized from benzyl 2-acetamido-2-deoxy-5, 6-O-isopropylidene-beta-D-glucofuran...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00351a005
更新日期：1982-09-01 00:00:00
abstract：:Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or ary...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950592+
更新日期：1996-02-16 00:00:00
abstract：:The low oral bioavailability and rapid biliary excretion of peptide-derived HIV protease inhibitors have limited their utility as potential therapeutic agents. Our broad screening program to discover nonpeptidic HIV protease inhibitors had previously identified compound II (phenprocoumon, K(i) = 1 muM) as a lead templ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00018a023
更新日期：1995-09-01 00:00:00
abstract：:Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900340a
更新日期：2009-11-26 00:00:00
abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00164a021
更新日期：1990-02-01 00:00:00
abstract：:A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4009532
更新日期：2013-11-14 00:00:00
abstract：:1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00128a023
更新日期：1989-08-01 00:00:00
abstract：:Rhenium-cyclized CCMSH analogues are novel melanoma-targeting metallopeptides with high tumor uptake, long tumor retention, and low background in normal tissues, which make these metallopeptides an ideal structural motif for designing novel melanoma-targeting agents. ReCCMSH has been derivatized with a 1,4,7,10-tetraa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010408m
更新日期：2002-07-04 00:00:00
abstract：:The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060435i
更新日期：2006-08-10 00:00:00
abstract：:Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid dis...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401543h
更新日期：2013-12-27 00:00:00
abstract：:Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01170
更新日期：2015-11-12 00:00:00
abstract：:The response profiles of 36 para-substituted diphenylethylenes (DPEs) and triphenylacrylonitriles (TPEs) have been compared by multivariate analysis. The responses measured were (a) relative binding affinity (RBA) for the cytosol estrogen receptor (ER), (b) ability to promote the growth of the human MCF7 breast cancer...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00081a021
更新日期：1992-02-07 00:00:00
abstract：:Penicillin-binding proteins represent well-established, validated, and still very promising targets for the design and development of new antibacterial agents. The transglycosylase domain of penicillin-binding proteins is especially important, as it catalyzes polymerization of glycan chains, using the peptidoglycan pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01482
更新日期：2015-12-24 00:00:00
abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800944x
更新日期：2008-12-11 00:00:00
abstract：:Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9003297
更新日期：2009-06-25 00:00:00
abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1008743
更新日期：2010-11-11 00:00:00
abstract：:A new class of potential antitumor agents inspired by the enediyne antitumor antibiotics has been synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200289j
更新日期：2011-07-28 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：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060673d
更新日期：2006-10-05 00:00:00
abstract：:Autophagy is a lysosome-dependent mechanism of intracellular degradation for maintaining cellular homeostasis. Dysregulation of autophagy has been verified to be closely linked to a number of human diseases. Consequently, targeting autophagy has been highlighted as a novel therapeutic strategy for clinical utility. Mo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01019
更新日期：2018-06-14 00:00:00
abstract：:Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic disea...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00985
更新日期：2020-04-09 00:00:00
abstract：:WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991088y
更新日期：2000-02-10 00:00:00
abstract：:G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5002919
更新日期：2014-06-26 00:00:00
abstract：:A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00386a016
更新日期：1987-03-01 00:00:00
abstract：:c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm502018y
更新日期：2015-03-12 00:00:00
abstract：:The structure of azaprophen, which was originally assigned by 1H NMR analysis, was confirmed by X-ray crystallography. A comparison of 13C NMR isotropic chemical shift data for azaprophen in the solid state and in CDCl3 and DMSO-d6 solution was used to correlate solution and solid-state conformation as determined by t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00108a030
更新日期：1991-04-01 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
