Abstract：
:A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) in vitro. Against the P388 mouse leukemia in vivo, most of the analogues had activity comparable to actinomycin D and one was significantly more active. The results show that substitutions of this kind do not interfere with the antitumor activity of actinomycin D and may be useful for the design of modified actinomycin D analogues with greater selectivity.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Madhavarao MS,Chaykovsky M,Sengupta SKdoi
10.1021/jm00207a021subject
Has Abstractpub_date
1978-09-01 00:00:00pages
958-61issue
9eissn
0022-2623issn
1520-4804journal_volume
21pub_type
杂志文章abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00223a034
更新日期：1976-01-01 00:00:00
abstract：:The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesize...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01280
更新日期：2019-12-26 00:00:00
abstract：:The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4014136
更新日期：2013-12-12 00:00:00
abstract：:A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00015a012
更新日期：1995-07-21 00:00:00
abstract：:Peroxisome proliferator-activated receptor gamma (PPARgamma) is well-known as the receptor of thiazolidinedione antidiabetic drugs. In this paper, we present a successful example of employing structure-based virtual screening, a method that combines shape-based database search with a docking study and analogue search,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051129s
更新日期：2006-05-04 00:00:00
abstract：:Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioiso...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010949b
更新日期：2001-12-20 00:00:00
abstract：:Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection of resistant bacteria. Recently, conjugation of lipop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00818
更新日期：2016-10-27 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：:The 5-fluoro and 8-fluoro analogues of trimetoquinol, TMQ, have been synthesized and evaluated for beta 2- and beta 1-adrenoceptor activity in guinea pig trachea and atria, respectively. The fluoro analogues of TMQ maintained potent beta 2-adrenoceptor agonist activity but had reduced beta 1-adrenoceptor agonist activ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a015
更新日期：1987-01-01 00:00:00
abstract：:The nortropane cocaine analogue, 2beta-carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]nortropane (ZIENT), is a high affinity, selective serotonin transporter (SERT) ligand that has shown promise as a SERT imaging agent for single photon computed tomography (SPECT) when labeled with I-123. Synthesis of the labeling p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050799v
更新日期：2006-02-09 00:00:00
abstract：:When cephalosporins exert their biological activity by reacting with bacterial enzymes, opening of the beta-lactam ring can lead to expulsion of the 3'-substituent. A series of cephalosporins was prepared in which antibacterial quinolones were linked to the 3'-position through a quaternary nitrogen. Like the 3'-ester-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00106a031
更新日期：1991-02-01 00:00:00
abstract：:Etoxadrol (2a), one of the eight possible optical isomers of 2-ethyl-2-phenyl-4-(2-piperidyl)-1,3-dioxolane, was synthesized from (S,S)-1-(2-piperidyl)-1,2-ethanediol, which was obtained from cleavage of dexoxadrol (1a, (S,S)-2,2-diphenyl-4-(2-piperidyl)-1,3-dioxolane). The absolute configuration of etoxadrol hydrochl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00120a004
更新日期：1988-12-01 00:00:00
abstract：:The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00222a024
更新日期：1977-12-01 00:00:00
abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990014j
更新日期：1999-07-15 00:00:00
abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00855
更新日期：2020-08-27 00:00:00
abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01750
更新日期：2019-03-28 00:00:00
abstract：:A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinitie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01293
更新日期：2016-03-10 00:00:00
abstract：:Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Alth...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00389a011
更新日期：1987-06-01 00:00:00
abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400438k
更新日期：2013-09-12 00:00:00
abstract：:Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00096a001
更新日期：1992-09-04 00:00:00
abstract：:A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cel...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020355o
更新日期：2003-02-27 00:00:00
abstract：:Quantitative structure-activity relationships of the Hansch-type were developed to account for inhibition of thymidine kinases from Herpes simplex viruses types 1 and 2 (HSV1,2) by N2-phenylguanines. Derivatives with meta and/or para substituents on the phenyl ring display a wide range of overlapping, but not identica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00094a007
更新日期：1992-08-07 00:00:00
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'-d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00350a024
更新日期：1982-08-01 00:00:00
abstract：:sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980212v
更新日期：1999-03-25 00:00:00
abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000083u
更新日期：2000-09-07 00:00:00
abstract：:Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501072b
更新日期：2014-12-26 00:00:00
abstract：:Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluor...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401764a
更新日期：2014-02-13 00:00:00
abstract：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00154a017
更新日期：1986-04-01 00:00:00
abstract：:A series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against Trypanosoma brucei rhodesiense STIB900 and Plasmodium falciparum K1. The dicationic diphenyl compounds exhibited the best activities with IC 50 values against T. b. rhodesiense and P. falciparum in the nanomolar range. Fiv...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm7013088
更新日期：2008-02-28 00:00:00
abstract：:Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970872k
更新日期：1998-12-17 00:00:00
