6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor.

abstract：:A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 microM). T...

journal_title：Journal of medicinal chemistry

authors： Stankiewicz-Drogoń A,Dörner B,Erker T,Boguszewska-Chachulska AM

更新日期：2010-04-22 00:00:00

abstract：:2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, aga...

journal_title：Journal of medicinal chemistry

authors： Das BP,Wallace RA,Boykin DW Jr

更新日期：1980-05-01 00:00:00

abstract：:MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methylt...

journal_title：Journal of medicinal chemistry

authors： Karatas H,Townsend EC,Bernard D,Dou Y,Wang S

更新日期：2010-07-22 00:00:00

abstract：:To provide practical means for rapidly scanning the extensive experimental combinatorial chemistry libraries now available for high-throughput screening (HTS), it is essential to establish computational virtual ligand screening (VLS) techniques to rapidly identify out of a large library all active compounds against a ...

journal_title：Journal of medicinal chemistry

authors： Floriano WB,Vaidehi N,Zamanakos G,Goddard WA 3rd

更新日期：2004-01-01 00:00:00

abstract：:A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity re...

journal_title：Journal of medicinal chemistry

authors： Combs DW,Reese K,Cornelius LA,Gunnet JW,Cryan EV,Granger KS,Jordan JJ,Demarest KT

更新日期：1995-12-08 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 00:00:00

abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

journal_title：Journal of medicinal chemistry

authors： Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

更新日期：2020-09-10 00:00:00

abstract：:As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate subst...

journal_title：Journal of medicinal chemistry

authors： Schiffler MA,Antonysamy S,Bhattachar SN,Campanale KM,Chandrasekhar S,Condon B,Desai PV,Fisher MJ,Groshong C,Harvey A,Hickey MJ,Hughes NE,Jones SA,Kim EJ,Kuklish SL,Luz JG,Norman BH,Rathmell RE,Rizzo JR,Seng TW,Thi

更新日期：2016-01-14 00:00:00

abstract：:We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in ...

journal_title：Journal of medicinal chemistry

authors： Henry SP,Fernandez TJ,Anand JP,Griggs NW,Traynor JR,Mosberg HI

更新日期：2019-04-25 00:00:00

abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...

journal_title：Journal of medicinal chemistry

authors： Conti P,De Amici M,De Sarro G,Rizzo M,Stensbøl TB,Bräuner-Osborne H,Madsen U,Toma L,De Micheli C

更新日期：1999-10-07 00:00:00

abstract：:The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the E...

journal_title：Journal of medicinal chemistry

authors： Minutolo F,Bertini S,Papi C,Carlson KE,Katzenellenbogen JA,Macchia M

更新日期：2001-11-22 00:00:00

abstract：:Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug ta...

journal_title：Journal of medicinal chemistry

authors： Monti E,Gariboldi M,Maiocchi A,Marengo E,Cassino C,Gabano E,Osella D

更新日期：2005-02-10 00:00:00

abstract：:A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound 13a (AV4...

journal_title：Journal of medicinal chemistry

authors： Ivachtchenko AV,Mitkin OD,Yamanushkin PM,Kuznetsova IV,Bulanova EA,Shevkun NA,Koryakova AG,Karapetian RN,Bichko VV,Trifelenkov AS,Kravchenko DV,Vostokova NV,Veselov MS,Chufarova NV,Ivanenkov YA

更新日期：2014-09-25 00:00:00

abstract：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...

journal_title：Journal of medicinal chemistry

authors： Vineberg JG,Wang T,Zuniga ES,Ojima I

更新日期：2015-03-12 00:00:00

abstract：:Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual in...

journal_title：Journal of medicinal chemistry

authors： Helal CJ,Kang Z,Hou X,Pandit J,Chappie TA,Humphrey JM,Marr ES,Fennell KF,Chenard LK,Fox C,Schmidt CJ,Williams RD,Chapin DS,Siuciak J,Lebel L,Menniti F,Cianfrogna J,Fonseca KR,Nelson FR,O'Connor R,MacDougall M,Mc

更新日期：2011-07-14 00:00:00

abstract：:Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracy...

journal_title：Journal of medicinal chemistry

authors： Magedov IV,Manpadi M,Slambrouck SV,Steelant WF,Rozhkova E,Przheval'skii NM,Rogelj S,Kornienko A

更新日期：2007-10-18 00:00:00

abstract：:The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...

journal_title：Journal of medicinal chemistry

authors： Chakravarty PK,Greenlee WJ,Parsons WH,Patchett AA,Combs P,Roth A,Busch RD,Mellin TN

更新日期：1989-08-01 00:00:00

abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...

journal_title：Journal of medicinal chemistry

authors： Audouze K,Nielsen EØ,Peters D

更新日期：2004-06-03 00:00:00

abstract：:An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC(50): 0.08 μM (K1, chloroquine and multidrug resistant strain) and 0.07 μM (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Co...

journal_title：Journal of medicinal chemistry

authors： González Cabrera D,Douelle F,Feng TS,Nchinda AT,Younis Y,White KL,Wu Q,Ryan E,Burrows JN,Waterson D,Witty MJ,Wittlin S,Charman SA,Chibale K

更新日期：2011-11-10 00:00:00

abstract：:2',3'-Epimino analogues of neamine, ribostamycin, and kanamycin B possessing little or no intrinsic antimicrobial activity were designed to enhance the activity of kanamycin A against bacterial strains that elaborate aminoglycoside 3'-phosphotransferases. Routes were devised for their synthesis from the parent antibio...

journal_title：Journal of medicinal chemistry

authors： Kumar V,Jones GS Jr,Blacksberg I,Remers WA,Misiek M,Pursiano TA

更新日期：1980-01-01 00:00:00

abstract：:C-terminally truncated fragments of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) were tested for their ability to stimulate amylase secretion from pancreatic acinar cells and relax precontracted mesenteric arteries. h-alpha-CGRP, h-alpha-CGRP (1-36), h-alpha-CGRP (1-35), and h-alpha-CGRP (1-34) were made...

journal_title：Journal of medicinal chemistry

authors： Smith DD,Li J,Wang Q,Murphy RF,Adrian TE,Elias Y,Bockman CS,Abel PW

更新日期：1993-08-20 00:00:00

abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...

journal_title：Journal of medicinal chemistry

authors： Melnick M,Reich SH,Lewis KK,Mitchell LJ Jr,Nguyen D,Trippe AJ,Dawson H,Davies JF 2nd,Appelt K,Wu BW,Musick L,Gehlhaar DK,Webber S,Shetty B,Kosa M,Kahil D,Andrada D

更新日期：1996-07-05 00:00:00

abstract：:Homology modeling of G-protein-coupled seven-transmembrane receptors (GPCRs) remains a challenge despite the increasing number of released GPCR crystal structures. This challenge can be attributed to the low sequence identity and structural diversity of the ligand-binding pocket of GPCRs. We have developed an optimize...

journal_title：Journal of medicinal chemistry

authors： Yoshikawa Y,Oishi S,Kubo T,Tanahara N,Fujii N,Furuya T

更新日期：2013-06-13 00:00:00

abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...

journal_title：Journal of medicinal chemistry

authors： Saunders J,Showell GA,Snow RJ,Baker R,Harley EA,Freedman SB

更新日期：1988-02-01 00:00:00

abstract：:Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule ...

journal_title：Journal of medicinal chemistry

authors： Niu Y,Wang M,Cao Y,Nimmagadda A,Hu J,Wu Y,Cai J,Ye XS

更新日期：2018-04-12 00:00:00

abstract：:The academic setting provides an environment that may foster success in the discovery of certain types of small molecule tools while proving less suitable in others. For example, small molecule probes for poorly understood systems, those that exploit a specific resident expertise, and those whose commercial return is ...

journal_title：Journal of medicinal chemistry

authors： Huryn DM,Resnick LO,Wipf P

更新日期：2013-09-26 00:00:00

abstract：:The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...

journal_title：Journal of medicinal chemistry

authors： Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

更新日期：2020-10-08 00:00:00

abstract：:Variation of the bridge linking the heterocyclic ring and p-aminobenzoyl-L-glutamate portions of our previously described classical 2,4-diaminofuro[2,3-d]pyrimidines 1 and 2 are reported as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) and as antitumor agents. Specifically -CH2CH2- and -CH...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Devraj R,McGuire JJ,Kisliuk RL

更新日期：1995-09-15 00:00:00

abstract：:In order to find a new class of anti-Helicobacter pylori (H. pylori) agents, a series of 4-[(3-acetamido)phenyl]-2-(substituted guanidino)thiazoles and some structurally rigid analoges were synthesized and evaluated for antimicrobial activity against H. pylori. Among the compounds obtained, high anti-H. pyrori activit...

journal_title：Journal of medicinal chemistry

authors： Katsura Y,Tomishi T,Inoue Y,Sakane K,Matsumoto Y,Morinaga C,Ishikawa H,Takasugi H

更新日期：2000-08-24 00:00:00

abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...

journal_title：Journal of medicinal chemistry

authors： Li X,Li Z,Wu X,Xiong Z,Yang T,Fu Z,Liu X,Tan X,Zhong F,Wan X,Wang D,Ding X,Yang R,Hou H,Li C,Liu H,Chen K,Jiang H,Zheng M

更新日期：2020-08-27 00:00:00