Substituted 1,3,4-thiadiazoles with anticonvulsant activity. 2. Aminoalkyl derivatives.

abstract：:There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Other...

journal_title：Journal of medicinal chemistry

authors： Betts HM,Milicevic Sephton S,Tong C,Awais RO,Hill PJ,Perkins AC,Aigbirhio FI

更新日期：2016-10-27 00:00:00

abstract：:(-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's d...

journal_title：Journal of medicinal chemistry

authors： Naidoo J,De Jesus-Cortes H,Huntington P,Estill S,Morlock LK,Starwalt R,Mangano TJ,Williams NS,Pieper AA,Ready JM

更新日期：2014-05-08 00:00:00

abstract：:Hepatitis C virus infection constitutes a serious health problem in need of more effective therapies. Nucleoside analogues with improved exposure, efficacy, and selectivity are recognized as likely key components of future HCV therapy. 2'-C-Methylguanosine triphosphate has been known as a potent inhibitor of HCV RNA p...

journal_title：Journal of medicinal chemistry

authors： McGuigan C,Gilles A,Madela K,Aljarah M,Holl S,Jones S,Vernachio J,Hutchins J,Ames B,Bryant KD,Gorovits E,Ganguly B,Hunley D,Hall A,Kolykhalov A,Liu Y,Muhammad J,Raja N,Walters R,Wang J,Chamberlain S,Henson G

更新日期：2010-07-08 00:00:00

abstract：:1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentration. Replacement of one phenyl ring of 1-[2-(diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings, such as 2-thien...

journal_title：Journal of medicinal chemistry

authors： De Martino G,La Regina G,Di Pasquali A,Ragno R,Bergamini A,Ciaprini C,Sinistro A,Maga G,Crespan E,Artico M,Silvestri R

更新日期：2005-06-30 00:00:00

abstract：:The melanocortin-3 (MC3) and melanocortin-4 (MC4) receptors regulate energy homeostasis, food intake, and associated physiological conditions. The melanocortin-4 receptor (MC4R) has been studied extensively. Less is known about specific physiological roles of the melanocortin-3 receptor (MC3R). A major obstacle to thi...

journal_title：Journal of medicinal chemistry

authors： Singh A,Dirain M,Witek R,Rocca JR,Edison AS,Haskell-Luevano C

更新日期：2013-04-11 00:00:00

abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Remers WA,Catino JJ

更新日期：1989-08-01 00:00:00

abstract：:Peptidoaminobenzophenones (1), terminal N-substituted peptidoaminobenzophenones (14), and acylglycylaminobenzophenones (16) were prepared as a novel series of ring-opened derivatives of 1,4-benzodiazepine. Z-Gly- and Z-Ala-N-methylaminobenzophenones (4) were treated with HBr-HOAc to give Gly- and Ala-N-methylaminobenz...

journal_title：Journal of medicinal chemistry

authors： Hirai K,Ishiba T,Sugimoto H,Fujishita T,Tsukinoki Y,Hirose K

更新日期：1981-01-01 00:00:00

abstract：:H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in parti...

journal_title：Journal of medicinal chemistry

authors： Cowart M,Faghih R,Curtis MP,Gfesser GA,Bennani YL,Black LA,Pan L,Marsh KC,Sullivan JP,Esbenshade TA,Fox GB,Hancock AA

更新日期：2005-01-13 00:00:00

abstract：:Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...

journal_title：Journal of medicinal chemistry

authors： Sham HL,Bolis G,Stein HH,Fesik SW,Marcotte PA,Plattner JJ,Rempel CA,Greer J

更新日期：1988-02-01 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and d...

journal_title：Journal of medicinal chemistry

authors： Siu M,Sengupta Ghosh A,Lewcock JW

更新日期：2018-09-27 00:00:00

abstract：:Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biologic drugs that inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis and oth...

journal_title：Journal of medicinal chemistry

authors： Dietrich JD,Longenecker KL,Wilson NS,Goess C,Panchal SC,Swann SL,Petros AM,Hobson AD,Ihle D,Song D,Richardson P,Comess KM,Cox PB,Dombrowski A,Sarris K,Donnelly-Roberts DL,Duignan DB,Gomtsyan A,Jung P,Krueger AC,Ma

更新日期：2021-01-14 00:00:00

abstract：:Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like na...

journal_title：Journal of medicinal chemistry

authors： Pasternak GW,Hahn EF

更新日期：1980-06-01 00:00:00

abstract：:Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is a serine/threonine kinase implicated in the regulation of many biological processes. A fragment-based lead discovery approach was used to generate potent and selective MAP4K4 inhibitors. The fragment hit pursued in this article had excellent ligand ef...

journal_title：Journal of medicinal chemistry

authors： Crawford TD,Ndubaku CO,Chen H,Boggs JW,Bravo BJ,Delatorre K,Giannetti AM,Gould SE,Harris SF,Magnuson SR,McNamara E,Murray LJ,Nonomiya J,Sambrone A,Schmidt S,Smyczek T,Stanley M,Vitorino P,Wang L,West K,Wu P,Ye W

更新日期：2014-04-24 00:00:00

abstract：:Toward developing new potential analgesics, this first structure-activity relationship study of opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH), a human peptide inhibiting enkephalin degradation, was performed. A systematic Ala scanning proved that Phe(3) is a key residue for neprilysin and aminopeptidase N (AP-N) ectoenkephalin...

journal_title：Journal of medicinal chemistry

authors： Rosa M,Arsequell G,Rougeot C,Calle LP,Marcelo F,Pinto M,Centeno NB,Jiménez-Barbero J,Valencia G

更新日期：2012-02-09 00:00:00

abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00

abstract：:Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in th...

journal_title：Journal of medicinal chemistry

authors： Watterson SH,De Lucca GV,Shi Q,Langevine CM,Liu Q,Batt DG,Beaudoin Bertrand M,Gong H,Dai J,Yip S,Li P,Sun D,Wu DR,Wang C,Zhang Y,Traeger SC,Pattoli MA,Skala S,Cheng L,Obermeier MT,Vickery R,Discenza LN,D'Arien

更新日期：2016-10-13 00:00:00

abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In genera...

journal_title：Journal of medicinal chemistry

authors： McKinney J,Fannin R,Jordan S,Chae K,Rickenbacher U,Pedersen L

更新日期：1987-01-01 00:00:00

abstract：:Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydr...

journal_title：Journal of medicinal chemistry

authors： Murugesan N,Gu Z,Stein PD,Bisaha S,Spergel S,Girotra R,Lee VG,Lloyd J,Misra RN,Schmidt J,Mathur A,Stratton L,Kelly YF,Bird E,Waldron T,Liu EC,Zhang R,Lee H,Serafino R,Abboa-Offei B,Mathers P,Giancarli M,Seymou

更新日期：1998-12-17 00:00:00

abstract：:A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl grou...

journal_title：Journal of medicinal chemistry

authors： Sohda S,Fujimoto M,Tamegai T,Hirose N

更新日期：1979-03-01 00:00:00

abstract：:The reaction of platinum salts with bis(naphthalimide), compound 1, yielded two Pt-bis(naphthalimide) complexes, compounds 2 and 3 which differ from each other in their leaving groups being 1,1-cyclobutane dicarboxylate or chloride, respectively. The testing of the cytotoxic activity of compounds 2 and 3 against sever...

journal_title：Journal of medicinal chemistry

authors： Pérez JM,López-Solera I,Montero EI,Brana MF,Alonso C,Robinson SP,Navarro-Ranninger C

更新日期：1999-12-30 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：:Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. This study presents a high-resolution X-ray structure of the competitive antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isox...

journal_title：Journal of medicinal chemistry

authors： Hogner A,Greenwood JR,Liljefors T,Lunn ML,Egebjerg J,Larsen IK,Gouaux E,Kastrup JS

更新日期：2003-01-16 00:00:00

abstract：:Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...

journal_title：Journal of medicinal chemistry

authors： Qu W,Kung MP,Hou C,Oya S,Kung HF

更新日期：2007-07-12 00:00:00

abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Deflorian F,Phan K,Gao ZG,Wan TC,Gizewski E,Auchampach JA,Jacobson KA

更新日期：2012-05-24 00:00:00

abstract：:A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4...

journal_title：Journal of medicinal chemistry

authors： Crespo MI,Pagès L,Vega A,Segarra V,López M,Doménech T,Miralpeix M,Beleta J,Ryder H,Palacios JM

更新日期：1998-10-08 00:00:00

abstract：:Developing methods to incorporate protein flexibility into structure-based drug design is an important challenge. Our approach uses multiple protein structures (MPS) to create a receptor-based pharmacophore model of the desired target. We have previously demonstrated the success of the method by applying it to human i...

journal_title：Journal of medicinal chemistry

authors： Meagher KL,Lerner MG,Carlson HA

更新日期：2006-06-15 00:00:00

abstract：:[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low p...

journal_title：Journal of medicinal chemistry

authors： Kohl B,Sturm E,Senn-Bilfinger J,Simon WA,Krüger U,Schaefer H,Rainer G,Figala V,Klemm K

更新日期：1992-03-20 00:00:00

abstract：:A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and ...

journal_title：Journal of medicinal chemistry

authors： Hirose N,Kuriyama S,Kato Y,Toyoshima S

更新日期：1976-02-01 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