Synthesis and structure-activity relationship of (lactamylvinyl)cephalosporins exhibiting activity against staphylococci, pneumococci, and enterococci.


:The synthesis and structure-activity relationships of a new class of vinylcephalosporins substituted with a lactamyl residue are described. These compounds show excellent activity against enterococci and retain the broad spectrum activity of third-generation cephalosporins such as ceftriaxone.


J Med Chem


Heinze-Krauss I,Angehrn P,Guerry P,Hebeisen P,Hubschwerlen C,Kompis I,Page MG,Richter HG,Runtz V,Stalder H,Weiss U,Wei CC




Has Abstract


1996-04-26 00:00:00














  • Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a N-(2-Aminophenyl)-benzamide Binding Unit.

    abstract::A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDA...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Marson CM,Matthews CJ,Atkinson SJ,Lamadema N,Thomas NS

    更新日期:2015-09-10 00:00:00

  • Structure-activity relationships and binding mode of styrylquinolines as potent inhibitors of HIV-1 integrase and replication of HIV-1 in cell culture.

    abstract::Our prior studies showed that polyhydroxylated styrylquinolines are potent HIV-1 integrase (IN) inhibitors that block the replication of HIV-1 in cell culture at nontoxic concentrations. To explore the mechanism of action of these inhibitors, various novel styrylquinoline derivatives were synthesized and tested agains...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zouhiri F,Mouscadet JF,Mekouar K,Desmaële D,Savouré D,Leh H,Subra F,Le Bret M,Auclair C,d'Angelo J

    更新日期:2000-04-20 00:00:00

  • Small atrial natriuretic peptide analogues: design, synthesis, and structural requirements for guanylate cyclase activation.

    abstract::Structure/activity studies on atrial natriuretic peptide ANP (1-28) have highlighted three portions of the native molecule as necessary for its biological responses. We have linked these three regions and excised the remaining segments to produce a family of small analogues (less than half the size of the parent) whic...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: von Geldern TW,Rockway TW,Davidsen SK,Budzik GP,Bush EN,Chu-Moyer MY,Devine EM Jr,Holleman WH,Johnson MC,Lucas SD

    更新日期:1992-03-06 00:00:00

  • Focus on the controversial activation of human iNKT cells by 4-deoxy analogue of KRN7000.

    abstract::4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lacône V,Hunault J,Pipelier M,Blot V,Lecourt T,Rocher J,Turcot-Dubois AL,Marionneau S,Douillard JY,Clément M,Le Pendu J,Bonneville M,Micouin L,Dubreuil D

    更新日期:2009-08-13 00:00:00

  • "Addition" and "Subtraction": Selectivity Design for Type II Maternal Embryonic Leucine Zipper Kinase Inhibitors.

    abstract::While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improv...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chen X,Giraldes J,Sprague ER,Shakya S,Chen Z,Wang Y,Joud C,Mathieu S,Chen CH,Straub C,Duca J,Hurov K,Yuan Y,Shao W,Touré BB

    更新日期:2017-03-09 00:00:00

  • Synthesis of steroidal nitrosoureas with antitumor activity.

    abstract::Four steroidal nitrosoureas with structures which may permit specific binding to estrogen receptor were synthesized. Inhibitory activity was observed against the growth of the DMBA-induced transplantable rat mammary tumor 13762. ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lam HY,Begleiter A,Goldenberg GJ,Wong CM

    更新日期:1979-02-01 00:00:00

  • Structure-function studies of peptides inhibiting the ribonucleotide reductase activity of herpes simplex virus type I.

    abstract::Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex vi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gaudreau P,Brazeau P,Richer M,Cormier J,Langlois D,Langelier Y

    更新日期:1992-01-24 00:00:00

  • Novel phosphate anthelmintics. 3. Alkyl and aryl 1-methyleneallyl phosphates, phosphonates, and phosphinates.

    abstract::A series of new highly chlorinated 1-methyleneallyl ("butadienyl") dialkyl phosphates and related phosphonates and phosphinates has been synthesized and assessed for anthelmintic activity in mice against the tapeworm Hymenolepis nana and the pinworm Syphacia obvelata. Highest activity was observed with diethyl 2,3,3-t...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pilgram K,Hass DK

    更新日期:1975-12-01 00:00:00

  • Gadolinium complex of DO3A-benzothiazole aniline (BTA) conjugate as a theranostic agent.

    abstract::A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

    更新日期:2013-10-24 00:00:00

  • Acyclic analogues of 2'-deoxynucleosides related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine as potential antiviral agents.

    abstract::A series of acyclic analogues of 2'-deoxynucleosides related in structure to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG, 1) have been synthesized and evaluated for antiviral activity against herpes simplex virus type 1 (F strain). Additionally, the ability of these analogues to function as substrates for the vir...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Martin JC,Jeffrey GA,McGee DP,Tippie MA,Smee DF,Matthews TR,Verheyden JP

    更新日期:1985-03-01 00:00:00

  • Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents.

    abstract::Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tong Y,Bouska JJ,Ellis PA,Johnson EF,Leverson J,Liu X,Marcotte PA,Olson AM,Osterling DJ,Przytulinska M,Rodriguez LE,Shi Y,Soni N,Stavropoulos J,Thomas S,Donawho CK,Frost DJ,Luo Y,Giranda VL,Penning TD

    更新日期:2009-11-12 00:00:00

  • Genome-wide computational and expression analyses reveal G-quadruplex DNA motifs as conserved cis-regulatory elements in human and related species.

    abstract::Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse, and rat promoters showed enrichment of sequence with potential to adopt G4 ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Verma A,Halder K,Halder R,Yadav VK,Rawal P,Thakur RK,Mohd F,Sharma A,Chowdhury S

    更新日期:2008-09-25 00:00:00

  • N-substituent modulation of opiate agonist/antagonist activity in resolved 3-methyl-3-(m-hydroxyphenyl)piperidines.

    abstract::A series of 3-methyl-3-(m-hydroxyphenyl)piperidines with N-substituent variations have been synthesized and resolved, and an X-ray crystal structure of one analogue was determined. The compounds have been characterized, pharmacologically, by detailed opiate receptor binding studies and determination of in vivo analges...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cheng A,Uyeno E,Polgar W,Toll L,Lawson JA,DeGraw JI,Loew G,Camerman A,Camerman N

    更新日期:1986-04-01 00:00:00

  • Selective inhibitors of monoamine oxidase. 2. Arylamide SAR.

    abstract::Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Harfenist M,Joyner CT,Mize PD,White HL

    更新日期:1994-06-24 00:00:00

  • Dihydrofuro[3,4-c]pyridinones as inhibitors of the cytolytic effects of the pore-forming glycoprotein perforin.

    abstract::Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the cor...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lena G,Trapani JA,Sutton VR,Ciccone A,Browne KA,Smyth MJ,Denny WA,Spicer JA

    更新日期:2008-12-11 00:00:00

  • Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones.

    abstract::A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chimirri A,De Sarro A,De Sarro G,Grasso S,Trimarchi GR,Zappalà M

    更新日期:1989-01-01 00:00:00

  • Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

    abstract::Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Dong Y,Wang X,Kamaraj S,Bulbule VJ,Chiu FC,Chollet J,Dhanasekaran M,Hein CD,Papastogiannidis P,Morizzi J,Shackleford DM,Barker H,Ryan E,Scheurer C,Tang Y,Zhao Q,Zhou L,White KL,Urwyler H,Charman WN,Matile H,Witt

    更新日期:2017-04-13 00:00:00

  • 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1.

    abstract::2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: van Wijngaarden I,Kruse CG,van Hes R,van der Heyden JA,Tulp MT

    更新日期:1987-11-01 00:00:00

  • Identification of highly selective inhibitors of collagenase-1 from combinatorial libraries of diketopiperazines.

    abstract::Thiol-containing diketopiperazines have been recently identified as novel heterocyclic inhibitors of matrix metalloproteinase (MMPs). The compounds described had similar activities against the MMPs collagenase-1 and gelatinase-B. An inhibitor that showed greater than 10-fold selectivity for collagenase-1 over gelatina...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Szardenings AK,Antonenko V,Campbell DA,DeFrancisco N,Ida S,Shi L,Sharkov N,Tien D,Wang Y,Navre M

    更新日期:1999-04-22 00:00:00

  • Chemogenomic Profiling of Human and Microbial FK506-Binding Proteins.

    abstract::FK506-binding proteins (FKBPs) are evolutionarily conserved proteins that display peptidyl-prolyl isomerase activities and act as coreceptors for immunosuppressants. Microbial macrophage-infectivity-potentiator (Mip)-type FKBPs can enhance infectivity. However, developing druglike ligands for FKBPs or Mips has proven ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pomplun S,Sippel C,Hähle A,Tay D,Shima K,Klages A,Ünal CM,Rieß B,Toh HT,Hansen G,Yoon HS,Bracher A,Preiser P,Rupp J,Steinert M,Hausch F

    更新日期:2018-04-26 00:00:00

  • Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity.

    abstract::The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

    更新日期:2016-10-13 00:00:00

  • Evidence of the preferential involvement of mu receptors in analgesia using enkephalins highly selective for peripheral mu or delta receptors.

    abstract::In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gacel G,Fournié-Zaluski MC,Fellion E,Roques BP

    更新日期:1981-10-01 00:00:00

  • Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

    abstract::Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Serpi M,Ferrari V,Pertusati F

    更新日期:2016-12-08 00:00:00

  • Pan Assay Interference Compounds (PAINS) and Other Promiscuous Compounds in Antifungal Research.

    abstract::Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Pouliot M,Jeanmart S

    更新日期:2016-01-28 00:00:00

  • Novel bioactive and stable neurotensin peptide analogues capable of delivering radiopharmaceuticals and molecular beacons to tumors.

    abstract::The prevalence of neurotensin receptor (NTR) in several human tumors makes it an attractive target for the delivery of cytotoxic drugs and imaging agents. Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth. Unfortunately, NT has a short plasma half-life, which hinders its use for in...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Achilefu S,Srinivasan A,Schmidt MA,Jimenez HN,Bugaj JE,Erion JL

    更新日期:2003-07-17 00:00:00

  • Synthesis, biological properties, and molecular modeling investigation of the first potent, selective, and water-soluble human A(3) adenosine receptor antagonist.

    abstract::A new, highly potent, selective, and water-soluble antagonist of the hA(3) adenosine receptor was synthesized and tested in binding and functional assays. Compound 4 (5-[[(4-pyridyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine hydrochloride) displayed high water solubility (...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Maconi A,Pastorin G,Da Ros T,Spalluto G,Gao ZG,Jacobson KA,Baraldi PG,Cacciari B,Varani K,Moro S,Borea PA

    更新日期:2002-08-15 00:00:00

  • Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection.

    abstract::The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Granberg KL,Yuan ZQ,Lindmark B,Edman K,Kajanus J,Hogner A,Malmgren M,O'Mahony G,Nordqvist A,Lindberg J,Tångefjord S,Kossenjans M,Löfberg C,Brånalt J,Liu D,Selmi N,Nikitidis G,Nordberg P,Hayen A,Aagaard A,Hansson E

    更新日期:2019-02-14 00:00:00

  • Non-nucleoside inhibitors of HIV-1 reverse transcriptase: molecular modeling and X-ray structure investigations.

    abstract::The structural features of a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors (3) are presented. Comparison of the structural and electronic properties with those of TIBO (1) and Nevirapine (2) yields a common three-dimensional model. This model permits the improvement of the lead compound 3 by chemi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Schäfer W,Friebe WG,Leinert H,Mertens A,Poll T,von der Saal W,Zilch H,Nuber B,Ziegler ML

    更新日期:1993-03-19 00:00:00

  • Synthesis and structure-activity relationships of potent new angiotensin converting enzyme inhibitors containing saturated bicyclic amino acids.

    abstract::The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfh...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Blankley CJ,Kaltenbronn JS,DeJohn DE,Werner A,Bennett LR,Bobowski G,Krolls U,Johnson DR,Pearlman WM,Hoefle ML

    更新日期:1987-06-01 00:00:00

  • Design of thymidylate synthase inhibitors using protein crystal structures: the synthesis and biological evaluation of a novel class of 5-substituted quinazolinones.

    abstract::The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-re...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Webber SE,Bleckman TM,Attard J,Deal JG,Kathardekar V,Welsh KM,Webber S,Janson CA,Matthews DA,Smith WW

    更新日期:1993-03-19 00:00:00