Synthesis and hypoglycemic activity of phenacyltriphenylphosphoranes and phosphonium salts.

abstract：:The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and...

journal_title：Journal of medicinal chemistry

authors： Millies B,von Hammerstein F,Gellert A,Hammerschmidt S,Barthels F,Göppel U,Immerheiser M,Elgner F,Jung N,Basic M,Kersten C,Kiefer W,Bodem J,Hildt E,Windbergs M,Hellmich UA,Schirmeister T

更新日期：2019-12-26 00:00:00

abstract：:Doxazosin analogues 1-3 and 1a were synthesized and investigated at alpha1-adrenoceptors and PC-3, DU-145, and LNCaP human prostate cancer cells. Compound 1 (cyclodoxazosin) was a potent alpha(1B)-adrenoceptor antagonist displaying antiproliferative activity higher than that of doxazosin in cancer cells in vitro and i...

journal_title：Journal of medicinal chemistry

authors： Giardinà D,Martarelli D,Sagratini G,Angeli P,Ballinari D,Gulini U,Melchiorre C,Poggesi E,Pompei P

更新日期：2009-08-13 00:00:00

abstract：:Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibit...

journal_title：Journal of medicinal chemistry

authors： Zhang Y,Feng J,Jia Y,Wang X,Zhang L,Liu C,Fang H,Xu W

更新日期：2011-04-28 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：:A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum a...

journal_title：Journal of medicinal chemistry

authors： Osei-Gyimah P,Archer S,Gillan MG,Kosterlitz HW

更新日期：1981-02-01 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：:A series of conjugated hyaluronic acid particles (HAP), composed of a hydrophobic anticancer drug core and hydrophilic cyclodextrin/hyaluronic acid shell, were prepared through self-assembling and characterized by (1)H NMR titration, electron microscopy, zeta potential, and dynamic light-scattering experiments. The na...

journal_title：Journal of medicinal chemistry

authors： Yang Y,Zhang YM,Chen Y,Chen JT,Liu Y

更新日期：2013-12-12 00:00:00

abstract：:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial t...

journal_title：Journal of medicinal chemistry

authors： Duan F,Li X,Cai S,Xin G,Wang Y,Du D,He S,Huang B,Guo X,Zhao H,Zhang R,Ma L,Liu Y,Du Q,Wei Z,Xing Z,Liang Y,Wu X,Fan C,Ji C,Zeng D,Chen Q,He Y,Liu X,Huang W

更新日期：2014-05-08 00:00:00

abstract：:A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...

journal_title：Journal of medicinal chemistry

authors： Andersen KE,Braestrup C,Grønwald FC,Jørgensen AS,Nielsen EB,Sonnewald U,Sørensen PO,Suzdak PD,Knutsen LJ

更新日期：1993-06-11 00:00:00

abstract：:The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compou...

journal_title：Journal of medicinal chemistry

authors： von Nussbaum F,Miller B,Wild S,Hilger CS,Schumann S,Zorbas H,Beck W,Steglich W

更新日期：1999-09-09 00:00:00

abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...

journal_title：Journal of medicinal chemistry

authors： Vaezi MF,Alam M,Sani BP,Rogers TS,Simpson-Herren L,Wille JJ,Hill DL,Doran TI,Brouillette WJ,Muccio DD

更新日期：1994-12-23 00:00:00

abstract：:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...

journal_title：Journal of medicinal chemistry

authors： Yuta K,Jurs PC

更新日期：1981-03-01 00:00:00

abstract：:The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and C...

journal_title：Journal of medicinal chemistry

authors： Hardcastle IR,Arris CE,Bentley J,Boyle FT,Chen Y,Curtin NJ,Endicott JA,Gibson AE,Golding BT,Griffin RJ,Jewsbury P,Menyerol J,Mesguiche V,Newell DR,Noble ME,Pratt DJ,Wang LZ,Whitfield HJ

更新日期：2004-07-15 00:00:00

abstract：:Tumor protein 53 (p53) is a critical regulator of cell cycle and apoptosis that is frequently disabled in human tumors. In many tumor types, p53 is deleted or mutated, but in others p53 is inactivated by overexpression or amplification of its negative regulator mouse double minute 2 (MDM2). A high-throughput screening...

journal_title：Journal of medicinal chemistry

authors： Allen JG,Bourbeau MP,Wohlhieter GE,Bartberger MD,Michelsen K,Hungate R,Gadwood RC,Gaston RD,Evans B,Mann LW,Matison ME,Schneider S,Huang X,Yu D,Andrews PS,Reichelt A,Long AM,Yakowec P,Yang EY,Lee TA,Oliner JD

更新日期：2009-11-26 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：:Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expe...

journal_title：Journal of medicinal chemistry

authors： Haginoya N,Kobayashi S,Komoriya S,Yoshino T,Suzuki M,Shimada T,Watanabe K,Hirokawa Y,Furugori T,Nagahara T

更新日期：2004-10-07 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：:Self-organizing maps were trained to separate high- and low-active propafenone-type inhibitors of P-glycoprotein. The trained maps were subsequently used to identify highly active compounds in a virtual screen of the SPECS compound library. ...

journal_title：Journal of medicinal chemistry

authors： Kaiser D,Terfloth L,Kopp S,Schulz J,de Laet R,Chiba P,Ecker GF,Gasteiger J

更新日期：2007-04-05 00:00:00

abstract：:The receptor CRM1 is responsible for the nuclear export of many tumor-suppressor proteins and viral ribonucleoproteins. This renders CRM1 an interesting target for therapeutic intervention in diverse cancer types and viral diseases. Structural studies of Saccharomyces cerevisiae CRM1 ( Sc ...

journal_title：Journal of medicinal chemistry

authors： Shaikhqasem A,Dickmanns A,Neumann P,Ficner R

更新日期：2020-07-23 00:00:00

abstract：:Mercapto derivatives of palmitic acid are capable of binding 99mTc. Based on the hypothesis that 99mTc-labeled palmitic acid derivatives would behave biologically like palmitic acid and thus could be used as myocardial imaging agents, three mercaptopalmitic acid derivatives have been prepared. The synthesis of 2-merca...

journal_title：Journal of medicinal chemistry

authors： Livni E,Davis MA,Warner VD

更新日期：1979-05-01 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：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...

journal_title：Journal of medicinal chemistry

authors： Rossi M

更新日期：1983-09-01 00:00:00

abstract：:Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecul...

journal_title：Journal of medicinal chemistry

authors： Bautista-Aguilera ÓM,Budni J,Mina F,Medeiros EB,Deuther-Conrad W,Entrena JM,Moraleda I,Iriepa I,López-Muñoz F,Marco-Contelles J

更新日期：2018-08-09 00:00:00

abstract：:Metal based therapeutics are a precious class of drugs in oncology research that include examples of theranostic drugs, which are active in both diagnostic, specifically imaging, and therapeutics applications. Ruthenium compounds have shown selective bioactivity and the ability to overcome the resistance that platinum...

journal_title：Journal of medicinal chemistry

authors： Thota S,Rodrigues DA,Crans DC,Barreiro EJ

更新日期：2018-07-26 00:00:00

abstract：:Glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) are proglucagon derived peptides that are released from gut endocrine cells in response to nutrient intake. These molecules are rapidly inactivated by the action of dipeptidyl peptidase IV (DPP-4) which limits their use as therapeutic agents. The rece...

journal_title：Journal of medicinal chemistry

authors： Suzuki R,Brown GA,Christopher JA,Scully CCG,Congreve M

更新日期：2020-02-13 00:00:00

abstract：:The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been...

journal_title：Journal of medicinal chemistry

authors： Cramer RD,Poss MA,Hermsmeier MA,Caulfield TJ,Kowala MC,Valentine MT

更新日期：1999-09-23 00:00:00

abstract：:Nitric oxide synthases (NOSs) comprise three closely related isoforms that catalyze the oxidation of L-arginine to L-citrulline and the important second messenger nitric oxide (NO). Pharmacological selective inhibition of neuronal NOS (nNOS) has the potential to be therapeutically beneficial in various neurodegenerati...

journal_title：Journal of medicinal chemistry

authors： Huang H,Li H,Martásek P,Roman LJ,Poulos TL,Silverman RB

更新日期：2013-04-11 00:00:00

abstract：:In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in ...

journal_title：Journal of medicinal chemistry

authors： Coy DH,Murphy WA,Sueiras-Diaz J,Coy EJ,Lance VA

更新日期：1985-02-01 00:00:00

abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...

journal_title：Journal of medicinal chemistry

authors： Asano N,Nishida M,Kato A,Kizu H,Matsui K,Shimada Y,Itoh T,Baba M,Watson AA,Nash RJ,Lilley PM,Watkin DJ,Fleet GW

更新日期：1998-07-02 00:00:00

abstract：:Fragment based drug discovery (FBDD) is a widely used tool for discovering novel therapeutics. NMR is a powerful means for implementing FBDD, and several approaches have been proposed utilizing (1)H-(15)N heteronuclear single quantum coherence (HSQC) as well as one-dimensional (1)H and (19)F NMR to screen compound mix...

journal_title：Journal of medicinal chemistry

authors： Jordan JB,Poppe L,Xia X,Cheng AC,Sun Y,Michelsen K,Eastwood H,Schnier PD,Nixey T,Zhong W

更新日期：2012-01-26 00:00:00