Abstract：
:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thiotriazolopyrimidiniums, and bicyclic thioimidazolopyrimidiniums as 3'-substituents were also studied; cephalosporins with quarternized pyrimidinium moieties have better antimicrobial activities than neuteral pyrimidine cephalosporins, and stabilization of the positive charge on the pyrimidinium moieties is essential for better activity. According to semiempirical PM3 calculations, amino and alkylthio substituents on the pyrimidinium rings play a major role in charge stabilization and delocalization.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm Kdoi
10.1021/jm00048a018subject
Has Abstractpub_date
1994-10-28 00:00:00pages
3828-33issue
22eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:A series of 10-ketomorphinan analogues were synthesized, and their binding affinity at all three opioid receptors was investigated. In most cases, high affinity at micro and kappa receptors, and lower affinity at delta receptor was observed, resulting in good selectivity for micro and kappa receptors. A wide range of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304156
更新日期：2004-01-01 00:00:00
abstract：:The heretofore unknown gamma-(m-carboxyanilide) and gamma-(m-boronoanillide) derivatives of methotrexate (MTX) and the gamma-(m-carboxyanilide) derivatives of aminopterin (AMT) were prepared and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of cell growth in culture with the aim of comparing...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00106a016
更新日期：1991-02-01 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：:(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm034073f
更新日期：2003-07-17 00:00:00
abstract：:Two novel analogues, N-[2-amino-4-ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid (2) and N-[2-amino-4-ethyl-6-methyl[(pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DH...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0203534
更新日期：2003-02-13 00:00:00
abstract：:A quantitative structure-activity relationship (QSAR) study was performed on a set of 49 negative allosteric modulators of AMPA receptor, acting as anticonvulsant agents, using multiple linear regression. The predictive ability of the resulting model was evaluated against a set of 12 compounds; the results showed good...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0310838
更新日期：2004-03-25 00:00:00
abstract：:The natural abundance 13C magnetic resonance spectra of a series of sulfonamide drugs(sulfanilamide, sulfaguanidine,sulfathiazole, sulfasuxidine, sulfadiazine, sulfamerazine, sulfamethiazine, and sulfapyridine) have been determined at 25.15 MHz employing the pulse Fourier transform technique. The chemical shefts have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00239a014
更新日期：1975-05-01 00:00:00
abstract：:Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped ve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0108754
更新日期：2001-10-25 00:00:00
abstract：:A series of 2,3-diaminopropionanilides was synthesized by acylation of mono- and disubstituted aniline derivatives with 2,3-dibromopropionyl chloride and subsequent amination with the appropriate secondary amines. The target compounds were evaluated in mice for antiarrhythmic efficacy against chloroform-induced tachyc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00141a008
更新日期：1981-09-01 00:00:00
abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm015545y
更新日期：2001-12-20 00:00:00
abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00089a023
更新日期：1992-05-29 00:00:00
abstract：:A general method for synthesis of 2 beta-alkenyl penam sulfones has been developed. The new compounds inhibited most of the common types of beta-lactamase. The level of activity depended very strongly on the nature of the substituent in the 2 beta-alkenyl group. The inhibited species formed with the beta-lactamase fro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9601967
更新日期：1996-09-13 00:00:00
abstract：:Protein arginine methyltransferases (PRMTs) play an important role in diverse biological processes. Among the nine known human PRMTs, PRMT3 has been implicated in ribosomal biosynthesis via asymmetric dimethylation of the 40S ribosomal protein S2 and in cancer via interaction with the DAL-1 tumor suppressor protein. H...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3018332
更新日期：2013-03-14 00:00:00
abstract：:Fragment-based docking was used to select a conformation for virtual screening from a molecular dynamics trajectory of the West Nile virus nonstructural 3 protease. This conformation was chosen from an ensemble of 100 molecular dynamics snapshots because it optimally accommodates benzene, the most common ring in known...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900448m
更新日期：2009-08-13 00:00:00
abstract：:A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and assessed for their anticancer activity on the drug-resistant pancreatic cancer cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing properties and anticancer activity against the pancreatic cancer model MiaPaCa-2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900960v
更新日期：2009-10-08 00:00:00
abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970414b
更新日期：1997-11-07 00:00:00
abstract：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00075a027
更新日期：1993-11-12 00:00:00
abstract：:A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a012
更新日期：1975-10-01 00:00:00
abstract：:The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901226j
更新日期：2009-11-12 00:00:00
abstract：:Syntheses of several new analogues of lyngbyatoxin A from a single common intermediate are described. These compounds bear a carbon chain at the 7-position of the indolactam V (ILV) nucleus which contains either a hydrophilic or a lipophilic group. The effect of these minor structural alterations on the ability of the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00112a017
更新日期：1991-08-01 00:00:00
abstract：:Generation of a three-dimensional pharmacophore model (hypothesis) that correlates the biological activity of a series of farnesyl protein transferase (FPT) inhibitors, exemplified by the prototype 1-(4-pyridylacetyl)- 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine, Sch 44342, 1,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970291v
更新日期：1997-12-05 00:00:00
abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00241a026
更新日期：1975-07-01 00:00:00
abstract：:Studies indicate that MAO-B is induced in peripheral inflammatory diseases. To target peripheral tissues using MAO-B inhibitors that do not permeate the blood-brain barrier (BBB) the MAO-B-selective inhibitor deprenyl was remodeled by replacing the terminal acetylene with a CO2H function, and incorporating a para-OCH2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01588
更新日期：2018-08-23 00:00:00
abstract：:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leuk...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00139a024
更新日期：1981-07-01 00:00:00
abstract：:Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00152a022
更新日期：1986-02-01 00:00:00
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
更新日期：1985-11-01 00:00:00
abstract：:Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00113a006
更新日期：1991-09-01 00:00:00
abstract：:A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituen...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00142a013
更新日期：1981-10-01 00:00:00
abstract：:This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00166a017
更新日期：1990-04-01 00:00:00
abstract：:3',4'-Dihydroxynomifensine, 8-amino-1,2,3,4-tetrahydro-4-(3,4-dihydroxyphenyl)-2-methylisoquinoli ne (1a), is an agonist of dopamine receptors in central and peripheral systems. Since this dopamine receptor agonist bears an asymmetric center at position 4, its synthesis and resolution were undertaken as part of a stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00367a006
更新日期：1984-01-01 00:00:00
