Abstract：
:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a number of in vitro and in vivo tumor cell systems. Very good increases in life spans of mice bearing mammary carcinoma were obtained by treatment with the N6-allyl, N6-isopropyl, and N6-propargyl analogues, respectively. In rats, the N6-allyl analogue slowed the rate of transplantable mammary tumor growth by one-fourth. The short-chain adenosine analogues are more active in the treatment of animal carcinomas than in the leukemia or sarcoma tumor cell systems.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Fleysher MH,Bernacki RJ,Bullard GAdoi
10.1021/jm00186a031subject
Has Abstractpub_date
1980-12-01 00:00:00pages
1448-52issue
12eissn
0022-2623issn
1520-4804journal_volume
23pub_type
杂志文章abstract：:Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701478a
更新日期：2008-06-26 00:00:00
abstract：:The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9005912
更新日期：2010-01-14 00:00:00
abstract：:Neutrophil serine proteases, proteinase 3 (PR3) and human neutrophil elastase (HNE), are considered as targets for chronic inflammatory diseases. Despite sharing high sequence similarity, the two enzymes have different substrate specificities and functions. While a plethora of HNE inhibitors exist, PR3 specific inhibi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500782s
更新日期：2014-11-26 00:00:00
abstract：:Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070383c
更新日期：2007-07-12 00:00:00
abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800965b
更新日期：2008-12-11 00:00:00
abstract：:Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the scree...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0700316
更新日期：2007-07-12 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：:A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000951n
更新日期：2000-10-05 00:00:00
abstract：:Acid ceramidase (AC) is an intracellular cysteine amidase that catalyzes the hydrolysis of the lipid messenger ceramide. By regulating ceramide levels in cells, AC may contribute to the regulation of cancer cell proliferation and senescence and to the response to cancer therapy. We recently identified the antitumoral ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301879g
更新日期：2013-05-09 00:00:00
abstract：:Tuberculosis (TB) is a major health problem worldwide. We herein report a new class of pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis (M. tuberculosis). Various 2'- or 3'-halogeno derivatives of pyrimidine nucleosides containing uracil, 5-fluorouracil, and thymine bases were synthesized and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100165w
更新日期：2010-05-27 00:00:00
abstract：:We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01342
更新日期：2020-12-10 00:00:00
abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991081g
更新日期：1999-10-07 00:00:00
abstract：:The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701467e
更新日期：2008-06-26 00:00:00
abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00138a013
更新日期：1981-06-01 00:00:00
abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00202a020
更新日期：1978-04-01 00:00:00
abstract：:A four-step synthesis of 2-chlorodopamine (2b) is presented as well as methods for the syntheses of the N-methyl, ethyl, and n-propyl analogues (2c-e). Compounds 2b and 2c were essentially equipotent to dopamine for increasing renal blood flow in anesthetized dogs that had been treated with the alpha-adrenergic antago...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00159a005
更新日期：1986-09-01 00:00:00
abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049786s
更新日期：2004-12-16 00:00:00
abstract：:We disclose the design of a novel series of cyanoguanidines that are potent (IC(50) approximately 10-100 nM) and selective (> or = 100-fold) P2X(7) receptor antagonists against the other P2 receptor subtypes such as the P2Y(2), P2X(4), and P2X(3). We also found that these P2X(7) antagonists effectively reduced nocicep...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8015848
更新日期：2009-05-28 00:00:00
abstract：:Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070467l
更新日期：2007-07-12 00:00:00
abstract：:Learning and memory deficits in Alzheimer's disease (AD) result from synaptic failure and neuronal loss, the latter caused in part by excitotoxicity and oxidative stress. A therapeutic approach is described that uses NO-chimeras directed at restoration of both synaptic function and neuroprotection. 4-Methylthiazole (M...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300353r
更新日期：2012-08-09 00:00:00
abstract：:Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980642l
更新日期：1999-04-08 00:00:00
abstract：:Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01356
更新日期：2016-12-08 00:00:00
abstract：:A number of 3-bromo-, 3-nitro-, and 3-ethoxycarbonyl-5,7-dialkylpyrazolo[1,5-a]pyrimidines were synthesized and screened as in vitro cAMP phosphodiesterase inhibitors. The condensation of 3-aminopyrazole with symmetrical beta-diketones (acetylacetone, heptane-3,5-dione, etc.) afforded symmetrical dialkylpyrazolo[1,5-a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00239a004
更新日期：1975-05-01 00:00:00
abstract：:The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01666
更新日期：2018-05-24 00:00:00
abstract：:The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00022a008
更新日期：1995-10-27 00:00:00
abstract：:A series of novel 1'-methylxanthene-9-spiro-4'-piperidines has been prepared in the search for opiate analgesics with improved pharmacological properties. It has been found that introduction of a hydroxyl group into the 4-position of the xanthenespiropiperidine nucleus produces a potent mu-opiate agonist. The structur...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00130a022
更新日期：1989-10-01 00:00:00
abstract：:In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a600
更新日期：1982-01-01 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：:G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400914r
更新日期：2013-08-22 00:00:00
abstract：:A physiologically based model for gastrointestinal transit and absorption in humans is presented. The model can be used to study the dependency of the fraction dose absorbed (F(abs)) of both neutral and ionizable compounds on the two main physicochemical input parameters (the intestinal permeability coefficient (P(int...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030999b
更新日期：2004-07-29 00:00:00
