Abstract：
:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-deoxy-5'-substituted-5-fluorouridine (FUrd) derivatives in an effort to obtain compounds that might have improved substrate interactions compared to 1 and thus possibly be better prodrugs of FUra. Three derivatives, 5'-O-tosyl-FUrd (13), 5'-O-mesyl-FUrd (14), and 5'-deoxy-5'-bromo-FUrd (15), had cytostatic activity against L1210 and CCRF-CEM leukemic cells in culture superior to that of 1. In preliminary in vivo antitumor studies against L1210 leukemic cells in mice, 5'-deoxy-5'-chloro-FUrd (4), 5'-O-mesyl-FUrd (14), an 5'-deoxy-5'-fluoro-FUrd (18) gave percent increases in life span of 64, 58, and 58, respectively, compared to a value of 20 for compound 1.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Ajmera S,Danenberg PVdoi
10.1021/jm00350a024subject
Has Abstractpub_date
1982-08-01 00:00:00pages
999-1002issue
8eissn
0022-2623issn
1520-4804journal_volume
25pub_type
杂志文章abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020143r
更新日期：2002-08-15 00:00:00
abstract：:Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01994
更新日期：2019-02-14 00:00:00
abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5010896
更新日期：2014-12-11 00:00:00
abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00242a013
更新日期：1975-08-01 00:00:00
abstract：:Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01621
更新日期：2020-04-23 00:00:00
abstract：:PAC1 receptor is abundant in the CNS and plays an important role in neuronal survival. To identify the molecular determinants and the conformational components responsible for the activation of the PAC1 receptor, we performed a SAR study focusing on the N-terminal domain of its endogenous ligand, PACAP. This approach ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900291j
更新日期：2009-05-28 00:00:00
abstract：:Three monomethylated derivatives of 4'-hydroxyacetanilide (acetaminophen) were prepared in order to compare their cytotoxic potential and analgesic activity with that of acetaminophen. Only 4'-hydroxy-N-methylacetanilide (N-methylacetaminophen) was devoid of cytotoxic effects to hepatic tissue of mice. Results of comp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00159a029
更新日期：1986-09-01 00:00:00
abstract：:Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the prese...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00245a005
更新日期：1975-11-01 00:00:00
abstract：:A series of novel nitroheterocyclic phosphoramidates has been evaluated for antitumor activity in murine and xenograft tumor models and for toxicity in mice. Significant increases in lifespan and long-term survivors were noted in L1210 leukemia and B16 melanoma models, and both complete and partial tumor regressions w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000359y
更新日期：2001-01-04 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501194p
更新日期：2014-11-26 00:00:00
abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031111m
更新日期：2004-06-03 00:00:00
abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101233f
更新日期：2011-01-13 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：:8-Methoxy-1-oxo-2,3-dihydro-1H-cyclopenta]a]naphthalene (4) was converted to the oxalyl derivative (7) by treatment with diethyl oxalate in the presence of sodium ethoxide. Compound 7 in the form of the sodium salt was alkylated with ethyl bromoacetate in DMF to 2-(carbethoxymethyl)-8-methoxy-1-oxo-2,3-dihydro-1H-cycl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00179a008
更新日期：1980-05-01 00:00:00
abstract：:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compoun...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501285x
更新日期：2015-01-22 00:00:00
abstract：:The 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compoun...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00083a009
更新日期：1992-03-06 00:00:00
abstract：:Pyrrolobenzoxazepinone (PBO) derivatives represent a new class of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTs) whose prototype is (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5]benzoxazepin-7(6H)- one (6). Docking studies based on the three-dimensional structure of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990150o
更新日期：1999-10-21 00:00:00
abstract：:A series of (8 beta)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N1-position in order to evaluate their effectiveness in blocking vascular 5HT2 receptors. The influence of both the N1 substituent and amide derivative proved to be of great importance on binding affinities t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00164a029
更新日期：1990-02-01 00:00:00
abstract：:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00184a002
更新日期：1980-10-01 00:00:00
abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00223a017
更新日期：1976-01-01 00:00:00
abstract：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049884d
更新日期：2004-10-07 00:00:00
abstract：:Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocyl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031089x
更新日期：2004-04-08 00:00:00
abstract：:We report on the design, synthesis, and evaluation of a series of furanyl-salicyl-nitroxide derivatives as effective chemical probes for second-site screening against phosphotyrosine phosphatases (PTPs) using NMR-based techniques. The compounds have been tested against a panel of PTPs to assess their ability to inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061481l
更新日期：2007-05-03 00:00:00
abstract：:The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel nucleoside modifications that combine structural elements of 2'-O-methoxyethyl re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801294h
更新日期：2009-01-08 00:00:00
abstract：:Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a009
更新日期：1991-07-01 00:00:00
abstract：:An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (R...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030378i
更新日期：2004-01-15 00:00:00
abstract：:Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a maste...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01426
更新日期：2017-12-14 00:00:00
abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200330s
更新日期：2011-07-28 00:00:00
abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00369a019
更新日期：1984-03-01 00:00:00
abstract：:The scaffold concept was applied to systematically determine, analyze, and compare core structures of kinase inhibitors. From publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematically extracted and organized taking activity data, structural relationships, and retrosynthetic ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501237k
更新日期：2015-01-08 00:00:00
