Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class by a focused library approach featuring 3D-pharmacophore similarity.

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：:Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p...

journal_title：Journal of medicinal chemistry

authors： Fási L,Di Meo F,Kuo CY,Stojkovic Buric S,Martins A,Kúsz N,Béni Z,Dékány M,Balogh GT,Pesic M,Wang HC,Trouillas P,Hunyadi A

更新日期：2019-02-14 00:00:00

abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

journal_title：Journal of medicinal chemistry

authors： Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

更新日期：2018-02-22 00:00:00

abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

更新日期：1984-03-01 00:00:00

abstract：:DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...

journal_title：Journal of medicinal chemistry

authors： Vo-Quang Y,Carniato D,Vo-Quang L,Lacoste AM,Neuzil E,Le Goffic F

更新日期：1986-04-01 00:00:00

abstract：:Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Van Aerschot A,Janssen G,Claes P,Balzarini J,De Clercq E,Herdewijn P

更新日期：1990-02-01 00:00:00

abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...

journal_title：Journal of medicinal chemistry

authors： Talamas FX,Abbot SC,Anand S,Brameld KA,Carter DS,Chen J,Davis D,de Vicente J,Fung AD,Gong L,Harris SF,Inbar P,Labadie SS,Lee EK,Lemoine R,Le Pogam S,Leveque V,Li J,McIntosh J,Nájera I,Park J,Railkar A,Rajyagur

更新日期：2014-03-13 00:00:00

abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...

journal_title：Journal of medicinal chemistry

authors： Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson ME

更新日期：1985-02-01 00:00:00

abstract：:We have recently reported the phosphodiesterase 10A (PDE10A) inhibitor 2-[4-[1-(2-[(18)F]fluoroethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenoxymethyl]-quinoline ([(18)F]1a) as a promising candidate for in vivo imaging using positron emission tomography (PET). We now describe the synthesis and biological evaluation of a ...

journal_title：Journal of medicinal chemistry

authors： Andrés JI,De Angelis M,Alcázar J,Iturrino L,Langlois X,Dedeurwaerdere S,Lenaerts I,Vanhoof G,Celen S,Bormans G

更新日期：2011-08-25 00:00:00

abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

journal_title：Journal of medicinal chemistry

authors： Khanna S,Sobhia ME,Bharatam PV

更新日期：2005-04-21 00:00:00

abstract：:The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resist...

journal_title：Journal of medicinal chemistry

authors： Grob NM,Schmid S,Schibli R,Behe M,Mindt TL

更新日期：2020-05-14 00:00:00

abstract：:Four chiral congeners of arachidonylethanolamide (anandamide) have been synthesized and evaluated for (a) their ability to bind to the cannabinoid receptor in rat forebrain membranes and (b) their pharmacological potency as measured by the compounds' ability to inhibit electrically-evoked contractions of the mouse vas...

journal_title：Journal of medicinal chemistry

authors： Abadji V,Lin S,Taha G,Griffin G,Stevenson LA,Pertwee RG,Makriyannis A

更新日期：1994-06-10 00:00:00

abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...

journal_title：Journal of medicinal chemistry

authors： T'ang A,Lien EJ,Lai MM

更新日期：1985-08-01 00:00:00

abstract：:The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antim...

journal_title：Journal of medicinal chemistry

authors： Pettit GR,Singh SB,Boyd MR,Hamel E,Pettit RK,Schmidt JM,Hogan F

更新日期：1995-05-12 00:00:00

abstract：:Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with lo...

journal_title：Journal of medicinal chemistry

authors： Heikkilä T,Ramsey C,Davies M,Galtier C,Stead AM,Johnson AP,Fishwick CW,Boa AN,McConkey GA

更新日期：2007-01-25 00:00:00

abstract：:Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to the discovery of structurally diverse TopoI inhibitors. From 23 compounds selected by virtual screening, a total of 14 compounds were found to be TopoI in...

journal_title：Journal of medicinal chemistry

authors： Dong G,Sheng C,Wang S,Miao Z,Yao J,Zhang W

更新日期：2010-11-11 00:00:00

abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and c...

journal_title：Journal of medicinal chemistry

authors： Ohashi M,Oyama T,Nakagome I,Satoh M,Nishio Y,Nobusada H,Hirono S,Morikawa K,Hashimoto Y,Miyachi H

更新日期：2011-01-13 00:00:00

abstract：:In an attempt to synthesize pentamidine-aplysinopsin hybrid molecule 25, a lead molecule 8 (containing Z-configured aplysinopsin moiety) was identified for antileishmanial activity. Optimization of lead 8 provided 24 (containing E-configured aplysinopsin) possessing 10 times more activity and 401-fold less toxicity th...

journal_title：Journal of medicinal chemistry

authors： Porwal S,Chauhan SS,Chauhan PM,Shakya N,Verma A,Gupta S

更新日期：2009-10-08 00:00:00

abstract：:Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection....

journal_title：Journal of medicinal chemistry

authors： Blake S,Thanissery R,Rivera AJ,Hixon MS,Lin M,Theriot CM,Janda KD

更新日期：2020-07-09 00:00:00

abstract：:Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex vi...

journal_title：Journal of medicinal chemistry

authors： Gaudreau P,Brazeau P,Richer M,Cormier J,Langlois D,Langelier Y

更新日期：1992-01-24 00:00:00

abstract：:A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imagin...

journal_title：Journal of medicinal chemistry

authors： Pirmettis IC,Papadopoulos MS,Chiotellis E

更新日期：1997-08-01 00:00:00

abstract：:A series of novel monoacylated vitamin C derivatives were chemically synthesized with a stable ascorbate derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and acid anhydrides in pyridine. Their solubility in organic phase, thermal stability, radical scavenging activity, and in vitro skin permeability was...

journal_title：Journal of medicinal chemistry

authors： Yamamoto I,Tai A,Fujinami Y,Sasaki K,Okazaki S

更新日期：2002-01-17 00:00:00

abstract：:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 co...

journal_title：Journal of medicinal chemistry

authors： Kukolja S,Pfeil JL,Draheim SE,Ott JL

更新日期：1985-12-01 00:00:00

abstract：:The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid-peptide conjugates (CAPs), demonstrating that valine-glycine dipeptide-derived CAP 3 is the most ...

journal_title：Journal of medicinal chemistry

authors： Yadav K,Kumar S,Mishra D,Asad M,Mitra M,Yavvari PS,Gupta S,Vedantham M,Ranga P,Komalla V,Pal S,Sharma P,Kapil A,Singh A,Singh N,Srivastava A,Thukral L,Bajaj A

更新日期：2019-02-28 00:00:00

abstract：:We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activit...

journal_title：Journal of medicinal chemistry

authors： Flouret G,Mahan K,Majewski T

更新日期：1992-02-21 00:00:00

abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...

journal_title：Journal of medicinal chemistry

authors： Kratz F,Warnecke A,Scheuermann K,Stockmar C,Schwab J,Lazar P,Drückes P,Esser N,Drevs J,Rognan D,Bissantz C,Hinderling C,Folkers G,Fichtner I,Unger C

更新日期：2002-12-05 00:00:00

abstract：:The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows p...

journal_title：Journal of medicinal chemistry

authors： Ma D,Jiang Y,Chen F,Gong LK,Ding K,Xu Y,Wang R,Ge A,Ren J,Li J,Li J,Ye Q

更新日期：2006-01-26 00:00:00

abstract：:The concept of covalent inhibition of c-Jun N-terminal kinase 3 (JNK3) was successfully transferred to our well validated pyridinylimidazole scaffold varying several structural features in order to deduce crucial structure-activity relationships. Joint targeting of the hydrophobic region I and methylation of imidazole...

journal_title：Journal of medicinal chemistry

authors： Muth F,El-Gokha A,Ansideri F,Eitel M,Döring E,Sievers-Engler A,Lange A,Boeckler FM,Lämmerhofer M,Koch P,Laufer SA

更新日期：2017-01-26 00:00:00

abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...

journal_title：Journal of medicinal chemistry

authors： Krieger V,Hamacher A,Gertzen CGW,Senger J,Zwinderman MRH,Marek M,Romier C,Dekker FJ,Kurz T,Jung M,Gohlke H,Kassack MU,Hansen FK

更新日期：2017-07-13 00:00:00

abstract：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...

journal_title：Journal of medicinal chemistry

authors： Lowbridge J,Manning M,Haldar J,Sawyer WH

更新日期：1977-01-01 00:00:00