Abstract：
:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Kukolja S,Pfeil JL,Draheim SE,Ott JLdoi
10.1021/jm00150a024subject
Has Abstractpub_date
1985-12-01 00:00:00pages
1903-6issue
12eissn
0022-2623issn
1520-4804journal_volume
28pub_type
杂志文章abstract：:Substituted 6-anilinouracils were found to be potent inhibitors of the replication-specific enzyme, DNA polymerase III, from Bacillus subtilis. Inhibition potency was maximized by inclusion of small alkyl groups or halogens in the meta and para positions of the phenyl ring; polar substituents decreased activity consi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00175a007
更新日期：1980-01-01 00:00:00
abstract：:The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low molecular mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low molecular mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00416
更新日期：2020-04-09 00:00:00
abstract：:The dopamine D(3) receptor is recognized as a potential therapeutic target for the treatment of various neurological and psychiatric disorders. Targetting high affinity and D(3) versus D(2) receptor-preferring ligands, the partial agonist BP 897 was taken as a lead structure. Variations in the spacer and the aryl moie...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030836n
更新日期：2003-08-28 00:00:00
abstract：:A series of novel 3-quinolinecarboxamides that are structurally similar to the quinolone class of antibacterial agents possess excellent antiherpetic properties. By modifying the quinoline ring at the 1-, 2-, 3-, and 7-positions, analogues were identified that have up to 5-fold increased HSV-2 plaque-reduction potency...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00063a008
更新日期：1993-05-28 00:00:00
abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00380a014
更新日期：1985-02-01 00:00:00
abstract：:A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00232a007
更新日期：1976-10-01 00:00:00
abstract：:Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960616s
更新日期：1996-10-25 00:00:00
abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990191k
更新日期：1999-10-07 00:00:00
abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200330s
更新日期：2011-07-28 00:00:00
abstract：:An extension of the Mannich reaction, in which aminomethylation of the five position of uracil, is reported. Thus, primary and secondary alkylamines and primary aromatic amines containing ring-activating groups led to the title compounds 3-10. Compound 11 in which the aromatic ring contains the ring-deactivating nitro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00224a032
更新日期：1976-02-01 00:00:00
abstract：:In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma w...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00698
更新日期：2020-07-23 00:00:00
abstract：:Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400652r
更新日期：2013-08-22 00:00:00
abstract：:In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0303711
更新日期：2004-02-26 00:00:00
abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00145a023
更新日期：1985-07-01 00:00:00
abstract：:Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3'-epi-thymidine, (+)-carbocyclic 3'-deoxy-3'-azidothymidine, (+)-carbocyclic 2,3'-O-anhydrothymidine, (+)-carbocyclic 3'-O,6'-methylenethymidine, and (+)-(6'S)-carbocyclic 6'-methylthymidine were synthesized in a stereospecific manner from comm...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00167a011
更新日期：1990-05-01 00:00:00
abstract：:Protein tyrosine phosphatases (PTPs) constitute a diverse family of enzymes that, together with protein tyrosine kinases, control the level of intracellular tyrosine phosphorylation, thus regulating many cellular functions. PTP1B negatively regulates insulin signaling, in part, by dephosphorylating key tyrosine residu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm011100y
更新日期：2002-04-25 00:00:00
abstract：:N, N'-dihydroxybenzamdine represents a model compound for a new prodrug principle to improve the oral bioavailability of drugs containing amidine functions. The activation of the prodrug could be demonstrated in vitro by porcine and human subcellular enzyme fractions, the mitochondrial benzamidoxime reducing system, a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701259d
更新日期：2007-12-27 00:00:00
abstract：:Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00114a005
更新日期：1991-10-01 00:00:00
abstract：:Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00576
更新日期：2019-08-08 00:00:00
abstract：:On the basis of the remarkable biological similarities between hycanthone and oxamniquine and as a sequel to our finding that some esters of hycanthone are active against hycanthone-resistant schistosomes, we prepared oxamniquine acetate, oxamniquine N-methylcarbamate, and four substituted phenylsulfonohydrazones of o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00403a024
更新日期：1988-08-01 00:00:00
abstract：:Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, Mycobacterium tuberculosis (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) rende...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01187
更新日期：2019-10-24 00:00:00
abstract：:omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960493b
更新日期：1997-01-31 00:00:00
abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960092w
更新日期：1996-07-05 00:00:00
abstract：:In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4016137
更新日期：2013-12-27 00:00:00
abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5010896
更新日期：2014-12-11 00:00:00
abstract：:Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these di...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990316l
更新日期：1999-11-04 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：:A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characte...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100481d
更新日期：2010-07-08 00:00:00
abstract：:The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01128
更新日期：2020-10-08 00:00:00
abstract：:A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibac...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00113a026
更新日期：1991-09-01 00:00:00
