当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Comparative structure-activity relationships of antifolate triazines inhibiting murine tumor cells sensitive and resistant to methotrexate.

Comparative structure-activity relationships of antifolate triazines inhibiting murine tumor cells sensitive and resistant to methotrexate.

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 triazines are much more inhibitory against resistant cells than methotrexate or hydrophilic triazines. The results are compared with the behavior of other antifolate drugs that have been used in chemotherapy, as well as with eight antitumor drugs that are not antifolates. The acquired resistance of these cells toward hydrophilic antifolates may be attributed to the combined effect of an impaired active-transport system, a change in the conformation of dihydrofolate reductase in the resistant cells, and an amplified production of dihydrofolate reductase in the resistant cells.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

doi

10.1021/jm00369a019

subject

Has Abstract

pub_date

1984-03-01 00:00:00

pages

347-57

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

27

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach.

    abstract：:We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030862l

    authors： Berkhout TA,Blaney FE,Bridges AM,Cooper DG,Forbes IT,Gribble AD,Groot PH,Hardy A,Ife RJ,Kaur R,Moores KE,Shillito H,Willetts J,Witherington J

    更新日期：2003-09-11 00:00:00

  • New Insights into Human 17β-Hydroxysteroid Dehydrogenase Type 14: First Crystal Structures in Complex with a Steroidal Ligand and with a Potent Nonsteroidal Inhibitor.

    abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00293

    authors： Bertoletti N,Braun F,Lepage M,Möller G,Adamski J,Heine A,Klebe G,Marchais-Oberwinkler S

    更新日期：2016-07-28 00:00:00

  • Judging the significance of multiple linear regression models.

    abstract：:It is common practice to calculate large numbers of molecular descriptors, apply variable selection procedures to reduce the numbers, and then construct multiple linear regression (MLR) models with biological activity. The significance of these models is judged using the usual statistical tests. Unfortunately, these t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049111p

    authors： Livingstone DJ,Salt DW

    更新日期：2005-02-10 00:00:00

  • Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.

    abstract：:A series of pyridinyltetrahydropyridine derivatives was synthesized and evaluated as adrenoceptor and tetrabenazine antagonists. 4-(3-Fluoro-2-pyridinyl)-1,2,5,6-tetrahydropyridine proved to be the most potent and selective alpha 2-adrenoceptor antagonist of the series as measured in vitro by displacement of [3H]cloni...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00375a017

    authors： Saari WS,Halczenko W,Huff JR,Guare JP Jr,Hunt CA,Randall WC,Lotti VJ,Yarbrough GG

    更新日期：1984-09-01 00:00:00

  • Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acid: a new class of broad-spectrum antiviral agents.

    abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00381a004

    authors： De Clercq E,Holý A

    更新日期：1985-03-01 00:00:00

  • Thyroid hormone analogues. Synthesis of 3'-substituted 3,5-diiodo-L-thyronines and quantitative structure-activity studies of in vitro and in vivo thyromimetic activities in rat liver and heart.

    abstract：:Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00396a008

    authors： Leeson PD,Ellis D,Emmett JC,Shah VP,Showell GA,Underwood AH

    更新日期：1988-01-01 00:00:00

  • Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor.

    abstract：:N,N'-Diarylureas were prepared, and the structure-activity relationship relative to the CXCR2 receptor was examined. This led to the identification of a potent and highly selective CXCR2 antagonist, which in addition was shown to be functionally active both in vitro against human neutrophils and in vivo in rabbit mode...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm034248l

    authors： Widdowson KL,Elliott JD,Veber DF,Nie H,Rutledge MC,McCleland BW,Xiang JN,Jurewicz AJ,Hertzberg RP,Foley JJ,Griswold DE,Martin L,Lee JM,White JR,Sarau HM

    更新日期：2004-03-11 00:00:00

  • MolDock: a new technique for high-accuracy molecular docking.

    abstract：:In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm051197e

    authors： Thomsen R,Christensen MH

    更新日期：2006-06-01 00:00:00

  • Isothiazolopyridones: synthesis, structure, and biological activity of a new class of antibacterial agents.

    abstract：:We report the syntheses of first-generation derivatives of isothiazolopyridones and their in vitro evaluation as antibacterial agents. These compounds, containing a novel heterocyclic nucleus composed of an isothiazolone fused to a quinolizin-4-one (at C-2 and C-3 of the quinolizin-4-one), were prepared using a sequen...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm051066d

    authors： Wiles JA,Hashimoto A,Thanassi JA,Cheng J,Incarvito CD,Deshpande M,Pucci MJ,Bradbury BJ

    更新日期：2006-01-12 00:00:00

  • Reactions of artemisinin and arteether with acid: implications for stability and mode of antimalarial action.

    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

    authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

    更新日期：2006-10-05 00:00:00

  • Identification of N-[(5-{[(4-methylphenyl)sulfonyl]amino}-3-(trifluoroacetyl)-1H-indol-1-yl)acetyl]-l-leucine (NTRC-824), a neurotensin-like nonpeptide compound selective for the neurotensin receptor type 2.

    abstract：:Compounds acting via the neurotensin receptor type 2 (NTS2) are known to be active in animal models of acute and chronic pain. To identify novel NTS2 selective analgesics, we searched for NTS2 selective nonpeptide compounds using a FLIPR assay and identified the title compound (NTRC-824, 5) that, to our knowledge, is ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500857r

    authors： Thomas JB,Giddings AM,Wiethe RW,Olepu S,Warner KR,Sarret P,Gendron L,Longpre JM,Zhang Y,Runyon SP,Gilmour BP

    更新日期：2014-09-11 00:00:00

  • Steroidal affinity labels of the estrogen receptor. 2. 17 alpha-[(Haloacetamido)alkyl]estradiols.

    abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00013a011

    authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

    更新日期：1995-06-23 00:00:00

  • Synthesis and central nervous system evaluation of some 5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones.

    abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00217a019

    authors： Gogerty JH,Griot RG,Habeck D,Iorio LC,Houlihan WJ

    更新日期：1977-07-01 00:00:00

  • 3-substituted indole inhibitors against Francisella tularensis FabI identified by structure-based virtual screening.

    abstract：:In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4001242

    authors： Hu X,Compton JR,Abdulhameed MD,Marchand CL,Robertson KL,Leary DH,Jadhav A,Hershfield JR,Wallqvist A,Friedlander AM,Legler PM

    更新日期：2013-07-11 00:00:00

  • Discovery of 4-anilinofuro[2,3-b]quinoline derivatives as selective and orally active compounds against non-small-cell lung cancers.

    abstract：:We have reported the preparation and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinolines. However, drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by these compounds prompted us to search for newer derivatives. Among them, (E)-1-(4-(furo[2,3-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200046z

    authors： Chen YW,Chen YL,Tseng CH,Liang CC,Yang CN,Yao YC,Lu PJ,Tzeng CC

    更新日期：2011-07-14 00:00:00

  • Inactivation of monoamine oxidase B by analogues of the anticonvulsant agent milacemide (2-(n-pentylamino)acetamide).

    abstract：:Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00056a004

    authors： Nishimura K,Lu X,Silverman RB

    更新日期：1993-02-19 00:00:00

  • Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3).

    abstract：:PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is crucial for maturation of ribosomes and has been implicated in several diseases. We recently disclosed a highly potent, selective, and cell-active allosteric inhibitor of PRMT3, compound 4. Here, we report comprehensive struct...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01674

    authors： Kaniskan HÜ,Eram MS,Zhao K,Szewczyk MM,Yang X,Schmidt K,Luo X,Xiao S,Dai M,He F,Zang I,Lin Y,Li F,Dobrovetsky E,Smil D,Min SJ,Lin-Jones J,Schapira M,Atadja P,Li E,Barsyte-Lovejoy D,Arrowsmith CH,Brown PJ,Liu

    更新日期：2018-02-08 00:00:00

  • Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha.

    abstract：:A cell-free assay was developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0004749

    authors： Spencer TA,Li D,Russel JS,Collins JL,Bledsoe RK,Consler TG,Moore LB,Galardi CM,McKee DD,Moore JT,Watson MA,Parks DJ,Lambert MH,Willson TM

    更新日期：2001-03-15 00:00:00

  • Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors.

    abstract：:Selective inhibitors of human sirtuin 2 (SIRT2), a deacetylase, are candidate therapeutic agents for neurodegenerative diseases such as Parkinson's disease and Huntington's disease as well as potential tools for elucidating the biological functions of SIRT2. On the basis of homology models of SIRT1 and SIRT2, we desig...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3002108

    authors： Suzuki T,Khan MN,Sawada H,Imai E,Itoh Y,Yamatsuta K,Tokuda N,Takeuchi J,Seko T,Nakagawa H,Miyata N

    更新日期：2012-06-28 00:00:00

  • Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.

    abstract：:The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00014a023

    authors： Lakanen JR,Pegg AE,Coward JK

    更新日期：1995-07-07 00:00:00

  • Activity of B-nor analogues of neurosteroids on the GABA(A) receptor in primary neuronal cultures.

    abstract：:A GABA(A) receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-norallopregnanolone (i.e., 3alpha-hydroxy-7-nor-5alpha-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060002f

    authors： Suñol C,García DA,Bujons J,Kristofíková Z,Matyás L,Babot Z,Kasal A

    更新日期：2006-06-01 00:00:00

  • Isolation, structure, and functional elucidation of a modified pentapeptide, cysteine protease inhibitor (CPI-2081) from Streptomyces species 2081 that exhibit inhibitory effect on cancer cell migration.

    abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9014179

    authors： Singh JP,Tamang S,Rajamohanan PR,Jima NC,Chakraborty G,Kundu GC,Gaikwad SM,Khan MI

    更新日期：2010-07-22 00:00:00

  • Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

    abstract：:Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered cli...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.5b00326

    authors： Röhrig UF,Majjigapu SR,Vogel P,Zoete V,Michielin O

    更新日期：2015-12-24 00:00:00

  • 2-Amino-6-furan-2-yl-4-substituted nicotinonitriles as A2A adenosine receptor antagonists.

    abstract：:A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701594y

    authors： Mantri M,de Graaf O,van Veldhoven J,Göblyös A,von Frijtag Drabbe Künzel JK,Mulder-Krieger T,Link R,de Vries H,Beukers MW,Brussee J,Ijzerman AP

    更新日期：2008-08-14 00:00:00

  • Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1.

    abstract：:As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cyto...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01669

    authors： Alverez CN,Park JE,Toti KS,Xia Y,Krausz KW,Rai G,Bang JK,Gonzalez FJ,Jacobson KA,Lee KS

    更新日期：2020-11-25 00:00:00

  • Synthesis and some pharmacological properties (4-beta-(2-thienyl)-L-alanine)oxytocin.

    abstract：:The synthesis and some biological activities of [4-beta-(2-thienyl)-L-alanine]oxytocin are reported. This analogue has been studied in an ongoing exploration of the biological effects of introducing amino acid residues with bulky hydrophobic side chains into the second corner position of the beta turn present in the c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00199a022

    authors： Smith CW,Skala G,Walter R

    更新日期：1978-01-01 00:00:00

  • 2-Fluoroformycin and 2-aminoformycin. Synthesis and biological activity.

    abstract：:Syntheses of 2-fluoroformycin [7-amino-5-fluoro-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2b) and 2-aminoformycin [5,7-diamino-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2c) are described. Cytotoxicity data are given for 2b and 2c alone as well as with added pentostatin. Kinetic parameters for adeno...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00149a033

    authors： Secrist JA 3rd,Shortnacy AT,Montgomery JA

    更新日期：1985-11-01 00:00:00

  • Synthesis and biological activity of highly active alpha-aza analogues of luliberin.

    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

    authors： Dutta AS,Furr BJ,Giles MB,Valcaccia B

    更新日期：1978-10-01 00:00:00

  • Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.

    abstract：:A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm7014777

    authors： Kiss R,Kiss B,Könczöl A,Szalai F,Jelinek I,László V,Noszál B,Falus A,Keseru GM

    更新日期：2008-06-12 00:00:00

  • Benzothiadiazine dioxide dibenzyl derivatives as potent human cytomegalovirus inhibitors: synthesis and comparative molecular field analysis.

    abstract：:The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-don...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000033p

    authors： Martinez A,Gil C,Abasolo MI,Castro A,Bruno AM,Perez C,Prieto C,Otero J

    更新日期：2000-08-24 00:00:00