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

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

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

更新日期：2015-09-10 00:00:00

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

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

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

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

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

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

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

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

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

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

更新日期：1979-02-01 00:00:00

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

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

更新日期：1992-01-24 00:00:00

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

authors： Pilgram K,Hass DK

更新日期：1975-12-01 00:00:00

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

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

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

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

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

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

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

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

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

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

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

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

更新日期：1994-06-24 00:00:00

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

更新日期：1981-10-01 00:00:00

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

authors： Serpi M,Ferrari V,Pertusati F

更新日期：2016-12-08 00:00:00

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

authors： Pouliot M,Jeanmart S

更新日期：2016-01-28 00:00:00

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

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

更新日期：2003-07-17 00:00:00

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

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

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

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

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

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

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

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

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

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