Abstract：
:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal helix-coil transition profile of poly(dA-dT) show extremely high affinity for helical DNA, with details of the binding interaction depending on the length and composition of the connecting chain. The ability of the compounds to inhibit nucleic acid synthesis in L1210 cell culture also differed significantly, as did their antitumor effects against P388 leukemia and B16 melanoma. Compound 2, with 10 methylene groups in the connecting chain, is 5-20 times as potent as ethidium against murine P388 leukemia. These results clearly illustrate the advantage gained by incorporating a weak antitumor agent in a double-intercalating analogue.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kuhlmann KF,Mosher CWdoi
10.1021/jm00143a014subject
Has Abstractpub_date
1981-11-01 00:00:00pages
1333-7issue
11eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S-propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00179a019
更新日期：1980-05-01 00:00:00
abstract：:A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determine...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00167a030
更新日期：1990-05-01 00:00:00
abstract：:Oxadiazoles are five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom, and they exist in different regioisomeric forms. Oxadiazoles are frequently occurring motifs in druglike molecules, and they are often used with the intention of being bioisosteric replacements for ester and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2013248
更新日期：2012-03-08 00:00:00
abstract：:The ghrelin receptor displays a high constitutive activity suggested to be involved in the regulation of appetite and food intake. Here, we have created peptides with small changes in the core binding motif -wFw- of the hexapeptide KwFwLL-NH(2) that can swap the peptide behavior from inverse agonism to agonism, indica...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300414b
更新日期：2012-09-13 00:00:00
abstract：:In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00115
更新日期：2015-04-09 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
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
更新日期：2006-06-01 00:00:00
abstract：:The alpha- and beta-D-lyxofuranosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. The alpha anomers were prepared by glycosylation of purine and pyrimidine aglycons with tetra-O-acetyl-alpha-D-lyxofuranose, followed by removal of the blocking groups. Th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00389a005
更新日期：1987-06-01 00:00:00
abstract：:A series of analogues of buspirone was synthesized in which modifications were made in the aryl moiety, alkylene chain length, and cyclic imide portion of the molecule. These compounds were tested in vitro for their binding affinities to rat brain membrane sites labeled by either the dopamine antagonist [3H]spiperone ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00356a014
更新日期：1983-02-01 00:00:00
abstract：:A series of 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]- 2,4-imidazolidinediones (6a-t) was synthesized, and the compounds were evaluated for direct skeletal muscle inhibition in the pithed rat gastrocnemius muscle preparation. The correctness of structural assignment of the new series was verified by alte...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00385a006
更新日期：1987-02-01 00:00:00
abstract：:Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Po...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1002556
更新日期：2010-09-23 00:00:00
abstract：:Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9014845
更新日期：2010-02-11 00:00:00
abstract：:Thymidylate synthase X (ThyX) represents an attractive target for tuberculosis drug discovery. Herein, we selected 16 compounds through a virtual screening approach. We solved the first X-ray crystal structure of Thermatoga maritima (Tm) ThyX in complex with a nonsubstrate analog inhibitor. Given the active site simil...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00977
更新日期：2016-10-13 00:00:00
abstract：:A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200249a
更新日期：2011-07-28 00:00:00
abstract：:Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501330g
更新日期：2015-01-22 00:00:00
abstract：:The first example of vinca derivatives 16-18 able to modulate P-glycoprotein (Pgp) efflux activity is reported. They were elaborated in two steps from vinorelbine 3 (VLN) by a modification of the velbenamine moiety. These compounds were able to decrease efficiently Pgp mediated influx and efflux of rhodamine-123 (Rho)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00525
更新日期：2016-12-08 00:00:00
abstract：:Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like na...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00180a019
更新日期：1980-06-01 00:00:00
abstract：:Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tubercu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00432
更新日期：2016-06-23 00:00:00
abstract：:The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01357
更新日期：2017-04-13 00:00:00
abstract：:6-Chloropurine derivatives of gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 3a, gamma-(Z)-ethylidene-2-methoxy-3-(4-nitro)benzyloxybutenolide 3b, gamma-(Z)-ethylidene-2-(4-nitro)benzyloxy-3-methoxybutenolide 3c, gamma-(Z)-ethylidene-2,3-di(4-nitro)benzyloxybutenolide 3d, and dimethylphosphono-gamma-(Z)-ethylidene-2,3-d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0004446
更新日期：2001-05-24 00:00:00
abstract：:The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure predictio...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050721e
更新日期：2006-01-26 00:00:00
abstract：:The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00137a006
更新日期：1981-05-01 00:00:00
abstract：:Androgens are well-known to stimulate prostate cancer (PC) growth. Thus, blockade of androgen production in testes and adrenals by CYP17 inhibition is a promising strategy for the treatment of PC. Moreover, many PC patients suffer from glucocorticoid overproduction, and importantly mutated androgen receptors can be st...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100317b
更新日期：2010-08-12 00:00:00
abstract：:Two series of halogenated sulfonamides have been prepared. The first consists of mono/dihalogenated sulfanilamides, whereas the second one consists of the mono/dihalogenated aminobenzolamides, incorporating equal or different halogens (F, Cl, Br, and I). These sulfonamides have been synthesized from the corresponding ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm021123s
更新日期：2003-05-22 00:00:00
abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061031t
更新日期：2006-12-28 00:00:00
abstract：:A class of new pyrimidinyl peptidomimetic agents (compounds 1-6) were synthesized, and their in vitro antimalarial activities against Plasmodium falciparum were evaluated. The core structure of the new agents consists of a substituted 5-aminopyrimidone ring and a Michael acceptor side chain methyl 2-hydroxymethyl-but-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020104f
更新日期：2002-08-01 00:00:00
abstract：:A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity. When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00118a024
更新日期：1988-10-01 00:00:00
abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00155a033
更新日期：1986-05-01 00:00:00
abstract：:The effect of a variety of aryl substituents on the potency and selectivity of 19 analogues of 1,3-dipropyl-8-phenylxanthine as antagonists at A1- and A2-adenosine receptors in brain tissue was determined. The 4-sulfamoylphenyl and 4-carbamoylphenyl analogues are potent and somewhat selective for the A1 receptor. None...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00158a034
更新日期：1986-08-01 00:00:00
abstract：:5-Nitronicotinamide (1) was prepared from 5-bromonicotinoyl chloride by treatment with ammonia and then oxidation with fuming H2SO4 and 30% H202. 2-Cholor-, 2-alkoxy-2-benzyloxy,2-phenoxy-,2-alkylamino-, and 2-benzylamino-5-nitronicatinamides were also prepared via 2-chloro-3-cyano-5-nitropyridine. 2-Methyl-5-nitronic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00211a027
更新日期：1977-01-01 00:00:00
