Spirocyclopropyl beta-lactams as mechanism-based inhibitors of serine beta-lactamases. Synthesis by rhodium-catalyzed cyclopropanation of 6-diazopenicillanate sulfone.

abstract：:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...

journal_title：Journal of medicinal chemistry

authors： Bijelic A,Theiner S,Keppler BK,Rompel A

更新日期：2016-06-23 00:00:00

abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

journal_title：Journal of medicinal chemistry

authors： Lövgren K,Hedberg A,Nilsson JL

更新日期：1981-04-01 00:00:00

abstract：:4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 microM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prost...

journal_title：Journal of medicinal chemistry

authors： Meanwell NA,Rosenfeld MJ,Trehan AK,Wright JJ,Brassard CL,Buchanan JO,Federici ME,Fleming JS,Gamberdella M,Zavoico GB

更新日期：1992-09-18 00:00:00

abstract：:Overexpression of myeloid cell leukemia-1 (Mcl-1) in cancers correlates with high tumor grade and poor survival. Additionally, Mcl-1 drives intrinsic and acquired resistance to many cancer therapeutics, including B cell lymphoma 2 family inhibitors, proteasome inhibitors, and antitubulins. Therefore, Mcl-1 inhibition ...

journal_title：Journal of medicinal chemistry

authors： Lee T,Christov PP,Shaw S,Tarr JC,Zhao B,Veerasamy N,Jeon KO,Mills JJ,Bian Z,Sensintaffar JL,Arnold AL,Fogarty SA,Perry E,Ramsey HE,Cook RS,Hollingshead M,Davis Millin M,Lee KM,Koss B,Budhraja A,Opferman JT,Kim K

更新日期：2019-04-25 00:00:00

abstract：:A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioa...

journal_title：Journal of medicinal chemistry

authors： Bailey TR,Rippin SR,Opsitnick E,Burns CJ,Pevear DC,Collett MS,Rhodes G,Tohan S,Huggins JW,Baker RO,Kern ER,Keith KA,Dai D,Yang G,Hruby D,Jordan R

更新日期：2007-04-05 00:00:00

abstract：:The possibility that catecholamines can be oxidized via aberrant pathways in vivo is open to question, but in vitro oxidation via aerobic manipulations is established. Assuming oxidation does occur, we have examined quantitatively the fast chemical reactions of the initial oxidation products, the o-quinones. The natur...

journal_title：Journal of medicinal chemistry

authors： Tse DC,McCreery RL,Adams RN

更新日期：1976-01-01 00:00:00

abstract：:Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. All were pan-agonists, binding to μ-, δ-,...

journal_title：Journal of medicinal chemistry

authors： Li Y,St Louis L,Knapp BI,Muthu D,Anglin B,Giuvelis D,Bidlack JM,Bilsky EJ,Polt R

更新日期：2014-03-27 00:00:00

abstract：:The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examine...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

更新日期：1986-09-01 00:00:00

abstract：:3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the ph...

journal_title：Journal of medicinal chemistry

authors： Cervetto L,Demontis GC,Giannaccini G,Longoni B,Macchia B,Macchia M,Martinelli A,Orlandini E

更新日期：1998-12-03 00:00:00

abstract：:Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-penta...

journal_title：Journal of medicinal chemistry

authors： Yamada S,Kawasaki M,Fujihara M,Watanabe M,Takamura Y,Takioku M,Nishioka H,Takeuchi Y,Makishima M,Motoyama T,Ito S,Tokiwa H,Nakano S,Kakuta H

更新日期：2019-10-10 00:00:00

abstract：:A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of the novel amidinoindole and benzofuran compounds, I and II. Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 29, which displayed an IC50 value o...

journal_title：Journal of medicinal chemistry

authors： Su T,Naughton MA,Smyth MS,Rose JW,Arfsten AE,McCowan JR,Jakubowski JA,Wyss VL,Ruterbories KJ,Sall DJ,Scarborough RM

更新日期：1997-12-19 00:00:00

abstract：:We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...

journal_title：Journal of medicinal chemistry

authors： Savechenkov PY,Zhang X,Chiara DC,Stewart DS,Ge R,Zhou X,Raines DE,Cohen JB,Forman SA,Miller KW,Bruzik KS

更新日期：2012-07-26 00:00:00

abstract：:The mTOR protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline 1, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin1), wh...

journal_title：Journal of medicinal chemistry

authors： Liu Q,Chang JW,Wang J,Kang SA,Thoreen CC,Markhard A,Hur W,Zhang J,Sim T,Sabatini DM,Gray NS

更新日期：2010-10-14 00:00:00

abstract：:Transient receptor potential canonical (TRPC) channels are highly homologous, nonselective cation channels that form many homo- and heterotetrameric channels. These channels are highly abundant in the brain and kidney and have been implicated in numerous diseases, such as depression, addiction, and chronic kidney dise...

journal_title：Journal of medicinal chemistry

authors： Sharma S,Hopkins CR

更新日期：2019-09-12 00:00:00

abstract：:The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-...

journal_title：Journal of medicinal chemistry

authors： Kaul M,Parhi AK,Zhang Y,LaVoie EJ,Tuske S,Arnold E,Kerrigan JE,Pilch DS

更新日期：2012-11-26 00:00:00

abstract：:HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first smal...

journal_title：Journal of medicinal chemistry

authors： Maga G,Falchi F,Garbelli A,Belfiore A,Witvrouw M,Manetti F,Botta M

更新日期：2008-11-13 00:00:00

abstract：:Recently we reported the synthesis of the first enantiomeric pair of irreversible opioid ligands [(3S,4R)-(-)- and (3R,4S)-(+)-cis-4, SUPERFIT] and specific interaction of the latter with the delta receptor. Here we report another enantiomeric pair of irreversible opioid ligands, (+)-trans- and (-)-trans-3-methylfenta...

journal_title：Journal of medicinal chemistry

authors： Kim CH,Rothman RB,Jacobson AE,Mattson MV,Bykov V,Streaty RA,Klee WA,George C,Long JB,Rice KC

更新日期：1989-06-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor central to fatty acid and glucose homeostasis. PPARγ is the molecular target for type 2 diabetes mellitus (T2DM) therapeutics TZDs (thiazolidinediones), full agonists of PPARγ with robust antidiabetic properties, which are confounded with signi...

journal_title：Journal of medicinal chemistry

authors： Frkic RL,He Y,Rodriguez BB,Chang MR,Kuruvilla D,Ciesla A,Abell AD,Kamenecka TM,Griffin PR,Bruning JB

更新日期：2017-06-08 00:00:00

abstract：:Methodology is presented for assembling fluorescently labeled bivalent molecules from monovalent constituents, without side chain protection or coupling agents. To illustrate the procedure, a series of bivalent peptidomimetics directed toward the Trk receptors were prepared and screened via fluorescent activated cell ...

journal_title：Journal of medicinal chemistry

authors： Pattarawarapan M,Reyes S,Xia Z,Zaccaro MC,Saragovi HU,Burgess K

更新日期：2003-08-14 00:00:00

abstract：:We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against ...

journal_title：Journal of medicinal chemistry

authors： De Castro S,García-Aparicio C,Andrei G,Snoeck R,Balzarini J,Camarasa MJ,Velázquez S

更新日期：2009-03-26 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

authors： Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

更新日期：2020-10-08 00:00:00

abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

journal_title：Journal of medicinal chemistry

authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

更新日期：1981-06-01 00:00:00

abstract：:The Free-Wilson equations are derived for the case of symmetrical substitution and are applied, in four modifications, to in vitro inhibitory activity of 77 organic disulfides against Histoplasma capsulatum. Substituent constants are listed to aid in the design of new inhibitory agents against this human pathogen (and...

journal_title：Journal of medicinal chemistry

authors： Schaad LJ,Werner RH,Dillon L,Field L,Tate CE

更新日期：1975-04-01 00:00:00

abstract：:In the treatment of cardiovascular diseases, it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin II formation, ensured by endothelial angiotensin-converting enzyme (ACE), with the diuretic and natriuretic responses due to the protection of the endogenou...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Coric P,Turcaud S,Rousselet N,Gonzalez W,Barbe B,Pham I,Jullian N,Michel JB,Roques BP

更新日期：1994-04-15 00:00:00

abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

journal_title：Journal of medicinal chemistry

authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

更新日期：1995-02-17 00:00:00

abstract：:The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothio...

journal_title：Journal of medicinal chemistry

authors： Showalter HD,Angelo MM,Berman EM,Kanter GD,Ortwine DF,Ross-Kesten SG,Sercel AD,Turner WR,Werbel LM,Worth DF

更新日期：1988-08-01 00:00:00

abstract：:Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effec...

journal_title：Journal of medicinal chemistry

authors： Yin QK,Wang CX,Wang YQ,Guo QL,Zhang ZL,Ou TM,Huang SL,Li D,Wang HG,Tan JH,Chen SB,Huang ZS

更新日期：2019-03-28 00:00:00

abstract：:Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, 2. Compound 2 is a potent an...

journal_title：Journal of medicinal chemistry

authors： Musso DL,Orr GF,Cochran FR,Kelley JL,Selph JL,Rigdon GC,Cooper BR,Jones ML

更新日期：2003-01-30 00:00:00

abstract：:New tuftsin/retro-tuftsin conjugates were designed and synthesized using a classical fluorenylmethoxycarbonyl (Fmoc) solid phase procedure. All the peptide conjugates were divided into three series: 1,4-dihydroxyanthraquinone (type A), 1-nitroacridine (type B), and 4-carboxyacridone (type C) derivatives. In type A con...

journal_title：Journal of medicinal chemistry

authors： Kukowska-Kaszuba M,Dzierzbicka K,Serocki M,Skladanowski A

更新日期：2011-04-14 00:00:00

abstract：:Inhibitors of adenosine deaminase (ADA, EC 3.5.4.4) are potential therapeutic agents for the treatment of various health disorders. Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities. We performed a SAR study involving a series of C2 or C8 substituted purine-riboside ...

journal_title：Journal of medicinal chemistry

authors： Gillerman I,Fischer B

更新日期：2011-01-13 00:00:00