New antiarrhythmic agents. 7. 2,3-Diaminopropionanilides.

abstract：:The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, i...

journal_title：Journal of medicinal chemistry

authors： Rivas FM,Stables JP,Murphree L,Edwankar RV,Edwankar CR,Huang S,Jain HD,Zhou H,Majumder S,Sankar S,Roth BL,Ramerstorfer J,Furtmüller R,Sieghart W,Cook JM

更新日期：2009-04-09 00:00:00

abstract：:The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular sub...

journal_title：Journal of medicinal chemistry

authors： Salvadori S,Bianchi C,Lazarus LH,Scaranari V,Attila M,Tomatis R

更新日期：1992-12-11 00:00:00

abstract：:The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

journal_title：Journal of medicinal chemistry

authors： Kumari S,Carmona AV,Tiwari AK,Trippier PC

更新日期：2020-11-12 00:00:00

abstract：:A new series of non-nucleoside reverse transcriptase inhibitors based on an imidazole-amide biarylether scaffold has been identified and shown to possess potent antiviral activity against HIV-1, including the NNRTI-resistant Y188L mutated virus. X-ray crystallography of inhibitors bound to reverse transcriptase, inclu...

journal_title：Journal of medicinal chemistry

authors： Chong P,Sebahar P,Youngman M,Garrido D,Zhang H,Stewart EL,Nolte RT,Wang L,Ferris RG,Edelstein M,Weaver K,Mathis A,Peat A

更新日期：2012-12-13 00:00:00

abstract：:Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in a...

journal_title：Journal of medicinal chemistry

authors： Vaccaro W,Amore C,Berger J,Burrier R,Clader J,Davis H,Domalski M,Fevig T,Salisbury B,Sher R

更新日期：1996-04-12 00:00:00

abstract：:A new paradigm for drug research has emerged, namely the deliberate search for molecules able to selectively affect the proliferation, differentiation, and migration of adult stem cells within the tissues in which they exist. Recently, there has been significant interest in medicinal chemistry toward the discovery and...

journal_title：Journal of medicinal chemistry

authors： Davies SG,Kennewell PD,Russell AJ,Seden PT,Westwood R,Wynne GM

更新日期：2015-04-09 00:00:00

abstract：:Leishmaniasis is an infection provoked by protozoans belonging to the genus Leishmania. Among the many species and subsepecies of such protozoa, Leishmania donovani chagasi causes visceral leishmaniasis. A β-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism, denominated here LdcCA. Ld...

journal_title：Journal of medicinal chemistry

authors： Syrjänen L,Vermelho AB,Rodrigues Ide A,Corte-Real S,Salonen T,Pan P,Vullo D,Parkkila S,Capasso C,Supuran CT

更新日期：2013-09-26 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging...

journal_title：Journal of medicinal chemistry

authors： Barrow JC,Stauffer SR,Rittle KE,Ngo PL,Yang Z,Selnick HG,Graham SL,Munshi S,McGaughey GB,Holloway MK,Simon AJ,Price EA,Sankaranarayanan S,Colussi D,Tugusheva K,Lai MT,Espeseth AS,Xu M,Huang Q,Wolfe A,Pietrak B,Z

更新日期：2008-10-23 00:00:00

abstract：:Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to o...

journal_title：Journal of medicinal chemistry

authors： Hiesinger K,Dar'in D,Proschak E,Krasavin M

更新日期：2021-01-14 00:00:00

abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...

journal_title：Journal of medicinal chemistry

authors： Kokotos G,Hsu YH,Burke JE,Baskakis C,Kokotos CG,Magrioti V,Dennis EA

更新日期：2010-05-13 00:00:00

abstract：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...

journal_title：Journal of medicinal chemistry

authors： Li S,Xu H,Cui S,Wu F,Zhang Y,Su M,Gong Y,Qiu S,Jiao Q,Qin C,Shan J,Zhang M,Wang J,Yin Q,Xu M,Liu X,Wang R,Zhu L,Li J,Xu Y,Jiang H,Zhao Z,Li J,Li H

更新日期：2016-07-28 00:00:00

abstract：:Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopy...

journal_title：Journal of medicinal chemistry

authors： Matsui T,Sugiura T,Nakai H,Iguchi S,Shigeoka S,Takada H,Odagaki Y,Nagao Y,Ushio Y,Ohmoto K

更新日期：1992-09-04 00:00:00

abstract：:A series of 2,2'-disubstituted 5,5'-dibenzimidazolyl ketones and related compounds have been synthesized of which 2,2'-bis(carbomethoxyamino)-5,5'-dibenzimidazolyl ketone exhibited a broad spectrum of anthelmintic activity in experimental animals. At doses of 10-50 mg/kg given intraperitoneally, 5 killed 100% of the a...

journal_title：Journal of medicinal chemistry

authors： Abuzar S,Sharma S,Fatma N,Gupta S,Murthy PK,Katiyar JC,Chatterjee RK,Sen AB

更新日期：1986-07-01 00:00:00

abstract：:LTX 109 is a synthetic antimicrobial peptidomimetic (SAMP) currently in clinical phase II trials for topical treatment of infections of multiresistant bacterial strains. All possible eight stereoisomers of the peptidomimetic have been synthesized and tested for antimicrobial effect, hemolysis, and hydrophobicity, reve...

journal_title：Journal of medicinal chemistry

authors： Isaksson J,Brandsdal BO,Engqvist M,Flaten GE,Svendsen JS,Stensen W

更新日期：2011-08-25 00:00:00

abstract：:Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptida...

journal_title：Journal of medicinal chemistry

authors： Poras H,Bonnard E,Dangé E,Fournié-Zaluski MC,Roques BP

更新日期：2014-07-10 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：:PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is crucial for maturation of ribosomes and has been implicated in several diseases. We recently disclosed a highly potent, selective, and cell-active allosteric inhibitor of PRMT3, compound 4. Here, we report comprehensive struct...

journal_title：Journal of medicinal chemistry

authors： Kaniskan HÜ,Eram MS,Zhao K,Szewczyk MM,Yang X,Schmidt K,Luo X,Xiao S,Dai M,He F,Zang I,Lin Y,Li F,Dobrovetsky E,Smil D,Min SJ,Lin-Jones J,Schapira M,Atadja P,Li E,Barsyte-Lovejoy D,Arrowsmith CH,Brown PJ,Liu

更新日期：2018-02-08 00:00:00

abstract：:It is common practice to calculate large numbers of molecular descriptors, apply variable selection procedures to reduce the numbers, and then construct multiple linear regression (MLR) models with biological activity. The significance of these models is judged using the usual statistical tests. Unfortunately, these t...

journal_title：Journal of medicinal chemistry

authors： Livingstone DJ,Salt DW

更新日期：2005-02-10 00:00:00

abstract：:Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound als...

journal_title：Journal of medicinal chemistry

authors： Su DS,Lim JJ,Tinney E,Wan BL,Young MB,Anderson KD,Rudd D,Munshi V,Bahnck C,Felock PJ,Lu M,Lai MT,Touch S,Moyer G,DiStefano DJ,Flynn JA,Liang Y,Sanchez R,Perlow-Poehnelt R,Miller M,Vacca JP,Williams TM,Anthony

更新日期：2009-11-26 00:00:00

abstract：:In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Vario...

journal_title：Journal of medicinal chemistry

authors： Yendapally R,Hurdle JG,Carson EI,Lee RB,Lee RE

更新日期：2008-03-13 00:00:00

abstract：:We previously described the discovery of GSK5852 (1), a non-nucleoside polymerase (NS5B) inhibitor of hepatitis C virus (HCV), in which an N-benzyl boronic acid was essential for potent antiviral activity. Unfortunately, facile benzylic oxidation resulted in a short plasma half-life (5 h) in human volunteers, and a ba...

journal_title：Journal of medicinal chemistry

authors： Chong PY,Shotwell JB,Miller J,Price DJ,Maynard A,Voitenleitner C,Mathis A,Williams S,Pouliot JJ,Creech K,Wang F,Fang J,Zhang H,Tai VW,Turner E,Kahler KM,Crosby R,Peat AJ

更新日期：2019-04-11 00:00:00

abstract：:The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl)thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on th...

journal_title：Journal of medicinal chemistry

authors： Janssens F,Torremans J,Janssen M,Stokbroekx RA,Luyckx M,Janssen PA

更新日期：1985-12-01 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

authors： Micheli F,Cavanni P,Andreotti D,Arban R,Benedetti R,Bertani B,Bettati M,Bettelini L,Bonanomi G,Braggio S,Carletti R,Checchia A,Corsi M,Fazzolari E,Fontana S,Marchioro C,Merlo-Pich E,Negri M,Oliosi B,Ratti E,Read K

更新日期：2010-07-08 00:00:00

abstract：:Selected derivatives of 9-oxo-1H,9H-benzothiopyrano[2,3-d]-1,2,3-triazole, a new heterocyclic ring system, and their S-oxides have been prepared and evaluated for antiallergic activity in the rat passive cutaneous anaphylaxis screen. Several of the compounds show intravenous potencies similar to or greater than that o...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Rockell CJ,Smith H,Spicer BA

更新日期：1984-02-01 00:00:00

abstract：:A series of compounds containing the 3-hydroxy-4H-pyran-4-one nucleus has been synthesized and tested as potential skeletal muscle relaxants. Reduction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (4) with HBr in HOAc--phenol yielded 2-(aminomethyl)-5-hydroxy-4H-pyran-4-one (kojic amine, 3) in 81% yield. Reaction of 2-...

journal_title：Journal of medicinal chemistry

authors： Atkinson JG,Girard Y,Rokach J,Rooney CS,McFarlane CS,Rackham A,Share NN

更新日期：1979-01-01 00:00:00

abstract：:Starting with a previously reported linear breast cancer targeting decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic peptide analogue cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized peptide with one d-amino acid (k) displayed higher uptake by breast cancer cells, with minimal uptake by the ...

journal_title：Journal of medicinal chemistry

authors： Raghuwanshi Y,Etayash H,Soudy R,Paiva I,Lavasanifar A,Kaur K

更新日期：2017-06-22 00:00:00

abstract：:N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both P...

journal_title：Journal of medicinal chemistry

authors： Rackham MD,Brannigan JA,Rangachari K,Meister S,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EW

更新日期：2014-03-27 00:00:00

abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...

journal_title：Journal of medicinal chemistry

authors： McBriar MD,Guzik H,Xu R,Paruchova J,Li S,Palani A,Clader JW,Greenlee WJ,Hawes BE,Kowalski TJ,O'Neill K,Spar B,Weig B

更新日期：2005-04-07 00:00:00

abstract：:Alkylation-elimination of adenine and 2-amino-6-chloropurine with gem-difluorocyclopropane dibromide 10 gave E- and Z-methylene-gem-difluorocyclopropanes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debenzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methylenecyclopropanes 4a, ...

journal_title：Journal of medicinal chemistry

authors： Wang R,Ksebati MB,Corbett TH,Kern ER,Drach JC,Zemlicka J

更新日期：2001-11-08 00:00:00