5,6-Cis-penems: broad-spectrum anti-methicillin-resistant Staphylococcus aureus beta-lactam antibiotics.

abstract：:The design and synthesis of 3-amino-2-oxo-4-phenylbutanoic acid amides (alpha-keto amides), a new class of aminopeptidase inhibitor, are described. These compounds, illustrated by the Phe-Leu analogue 2, are effective inhibitors of arginyl aminopeptidase (Ki = 1.5 microM), cytosol aminopeptidase (Ki = 1.0 microM), and...

journal_title：Journal of medicinal chemistry

authors： Ocain TD,Rich DH

更新日期：1992-02-07 00:00:00

abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Chaillet P,Soroca-Lucas E,Marçais-Collado H,Costentin J,Roques BP

更新日期：1983-01-01 00:00:00

abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...

journal_title：Journal of medicinal chemistry

authors： German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

更新日期：2011-10-27 00:00:00

abstract：:Fifteen quinolizidine derivatives have been tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. All compounds exhibited from moderate to high antiarrhythmic activity, and five of them (3, 4, 6, 13, and 15) were more active ...

journal_title：Journal of medicinal chemistry

authors： Tasso B,Budriesi R,Vazzana I,Ioan P,Micucci M,Novelli F,Tonelli M,Sparatore A,Chiarini A,Sparatore F

更新日期：2010-06-24 00:00:00

abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...

journal_title：Journal of medicinal chemistry

authors： Lin J,Deng H,Jin L,Pandey P,Quinn J,Cantin S,Rynkiewicz MJ,Gorga JC,Bibbins F,Celatka CA,Nagafuji P,Bannister TD,Meyers HV,Babine RE,Hayward NJ,Weaver D,Benjamin H,Stassen F,Abdel-Meguid SS,Strickler JE

更新日期：2006-12-28 00:00:00

abstract：:N-Aminated nucleoside complexes of cis-dichloroplatinum(II) were synthesized, and their antitumor activities against L1210 cells in mice and in vitro were studied. While the native nucleosides failed to show any antitumor activity, the complexes exhibited high antitumor activity and had no nephrotoxicity in mice. Stud...

journal_title：Journal of medicinal chemistry

authors： Maeda M,Abiko N,Uchida H,Sasaki T

更新日期：1984-04-01 00:00:00

abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...

journal_title：Journal of medicinal chemistry

authors： Burke TG,Mi Z

更新日期：1994-01-07 00:00:00

abstract：:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. ...

journal_title：Journal of medicinal chemistry

authors： Miyashita Y,Takahashi Y,Takayama C,Sumi K,Nakatsuka K,Ohkubo T,Abe H,Sasaki S

更新日期：1986-06-01 00:00:00

abstract：:A series of 3-(4-acylaminopiperazin-1-ylalkyl)indoles was synthesized and tested for antihypertensive activity. Compounds with no substituents in the indole portion of the molecule were generally most effective in lowering blood pressure in the spontaneous hypertensive rat model. Of these several analogues were very p...

journal_title：Journal of medicinal chemistry

authors： Glamkowski EJ,Reitano PA,Woodward DL

更新日期：1977-11-01 00:00:00

abstract：:Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray ...

journal_title：Journal of medicinal chemistry

authors： Kaldor SW,Kalish VJ,Davies JF 2nd,Shetty BV,Fritz JE,Appelt K,Burgess JA,Campanale KM,Chirgadze NY,Clawson DK,Dressman BA,Hatch SD,Khalil DA,Kosa MB,Lubbehusen PP,Muesing MA,Patick AK,Reich SH,Su KS,Tatlock JH

更新日期：1997-11-21 00:00:00

abstract：:Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their des...

journal_title：Journal of medicinal chemistry

authors： Heidtmann CV,Voukia F,Hansen LN,Sørensen SH,Urlund B,Nielsen S,Pedersen M,Kelawi N,Andersen BN,Pedersen M,Reinholdt P,Kongsted J,Nielsen CU,Klitgaard JK,Nielsen P

更新日期：2020-12-24 00:00:00

abstract：:N-(R)- and N-(S)-lactylsphingosine and their corresponding dihydrosphingosine derivatives were synthesized. The antileukemic activities of these compounds were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in human leukemia HL-60 cells. N-(R)- and N-(S)-Lactylsphingosine disp...

journal_title：Journal of medicinal chemistry

authors： Azuma H,Takao R,Shikata K,Niiro H,Tachibana T,Ogino K

更新日期：2003-07-31 00:00:00

abstract：:Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which all...

journal_title：Journal of medicinal chemistry

authors： Maurer PJ,Rapoport H

更新日期：1987-11-01 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

authors： Saavedra JE,Southan GJ,Davies KM,Lundell A,Markou C,Hanson SR,Adrie C,Hurford WE,Zapol WM,Keefer LK

更新日期：1996-10-25 00:00:00

abstract：:Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGF...

journal_title：Journal of medicinal chemistry

authors： Planken S,Behenna DC,Nair SK,Johnson TO,Nagata A,Almaden C,Bailey S,Ballard TE,Bernier L,Cheng H,Cho-Schultz S,Dalvie D,Deal JG,Dinh DM,Edwards MP,Ferre RA,Gajiwala KS,Hemkens M,Kania RS,Kath JC,Matthews J,Murra

更新日期：2017-04-13 00:00:00

abstract：:A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...

journal_title：Journal of medicinal chemistry

authors： Nishikawa Y,Shindo T,Ishii K,Nakamura H,Kon T,Uno H

更新日期：1989-03-01 00:00:00

abstract：:2-Amino-3-aroylthiophenes are agonist allosteric enhancers (AE) at the A(1) adenosine receptor (A(1)AR). Here we report the syntheses of three kinds of novel 2-aminothiophenes and assays of their AE activity at the human A(1)AR (hA(1)AR), namely, (1) 2-amino-4,5-diphenylthiophene-3-carboxylates, 3a-h, (2) 2-amino-3-be...

journal_title：Journal of medicinal chemistry

authors： Lütjens H,Zickgraf A,Figler H,Linden J,Olsson RA,Scammells PJ

更新日期：2003-05-08 00:00:00

abstract：:We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7...

journal_title：Journal of medicinal chemistry

authors： Nomoto Y,Takai H,Ohno T,Nagashima K,Yao K,Yamada K,Kubo K,Ichimura M,Mihara A,Kase H

更新日期：1996-01-05 00:00:00

abstract：:N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have ...

journal_title：Journal of medicinal chemistry

authors： Rackham MD,Brannigan JA,Moss DK,Yu Z,Wilkinson AJ,Holder AA,Tate EW,Leatherbarrow RJ

更新日期：2013-01-10 00:00:00

abstract：:As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown produc...

journal_title：Journal of medicinal chemistry

authors： Frieben EE,Amin S,Sharma AK

更新日期：2019-06-13 00:00:00

abstract：:Following the recent discoveries that some L-nucleosides are more or equal potent than their D-counterparts, we synthesized 2'-deoxy-2',2'-difluoro-L-erythro-pentofuranosyl nucleosides as potential antiviral agents. The target compounds were synthesized via the key intermediates 7a or 7b from L-gulono gamma-lactone. C...

journal_title：Journal of medicinal chemistry

authors： Kotra LP,Xiang Y,Newton MG,Schinazi RF,Cheng YC,Chu CK

更新日期：1997-10-24 00:00:00

abstract：:The synthesis and some biological activities of [4-beta-(2-thienyl)-L-alanine]oxytocin are reported. This analogue has been studied in an ongoing exploration of the biological effects of introducing amino acid residues with bulky hydrophobic side chains into the second corner position of the beta turn present in the c...

journal_title：Journal of medicinal chemistry

authors： Smith CW,Skala G,Walter R

更新日期：1978-01-01 00:00:00

abstract：:The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding...

journal_title：Journal of medicinal chemistry

authors： Van Dort M,Neubig R,Counsell RE

更新日期：1987-07-01 00:00:00

abstract：:High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identify...

journal_title：Journal of medicinal chemistry

authors： Pike KG,Morris J,Ruston L,Pass SL,Greenwood R,Williams EJ,Demeritt J,Culshaw JD,Gill K,Pass M,Finlay MR,Good CJ,Roberts CA,Currie GS,Blades K,Eden JM,Pearson SE

更新日期：2015-03-12 00:00:00

abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

journal_title：Journal of medicinal chemistry

authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

更新日期：1995-06-23 00:00:00

abstract：:A structure-activity study was carried out to determine the importance of the N-terminal amino acids of hCGRP8-37 in binding and antagonistic activity to CGRP receptors. Therefore, fragments of hCGRP8-37 as well as analogs obtained by the replacement of residues 9-12 by L-alanine were synthesized by solid-phase peptid...

journal_title：Journal of medicinal chemistry

authors： Mimeault M,Quirion R,Dumont Y,St-Pierre S,Fournier A

更新日期：1992-06-12 00:00:00

abstract：:A novel synthetic route to the cyclostellettamines 1 using as the key step a microwave-mediated macrocyclic ring-closing metathesis of precursors bispyridinium dienes 10 followed by catalytic hydrogenation has been developed. The open-chain bispyridinium dienes 10 showed uniformly higher histone deacetylase (HDAC) inh...

journal_title：Journal of medicinal chemistry

authors： Pérez-Balado C,Nebbioso A,Rodríguez-Graña P,Minichiello A,Miceli M,Altucci L,de Lera AR

更新日期：2007-05-17 00:00:00

abstract：:Structure-based macrocyclization of a 6-carboxylic acid indole chemotype has yielded potent and selective finger-loop inhibitors of the hepatitis C virus (HCV) NS5B polymerase. Lead optimization in conjunction with in vivo evaluation in rats identified several compounds showing (i) nanomolar potency in HCV replicon ce...

journal_title：Journal of medicinal chemistry

authors： Cummings MD,Lin TI,Hu L,Tahri A,McGowan D,Amssoms K,Last S,Devogelaere B,Rouan MC,Vijgen L,Berke JM,Dehertogh P,Fransen E,Cleiren E,van der Helm L,Fanning G,Nyanguile O,Simmen K,Van Remoortere P,Raboisson P,Vendev

更新日期：2014-03-13 00:00:00

abstract：:Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a m...

journal_title：Journal of medicinal chemistry

authors： Shimshoni JA,Bialer M,Wlodarczyk B,Finnell RH,Yagen B

更新日期：2007-12-13 00:00:00

abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...

journal_title：Journal of medicinal chemistry

authors： Choi SR,Pradhan A,Hammond NL,Chittiboyina AG,Tekwani BL,Avery MA

更新日期：2007-08-09 00:00:00