Synthesis and carcinogenic activity of oxidized benzacridines: potential metabolites of the strong carcinogen 7-methylbenz[c]acridine and of the inactive isomer 12-methylbenz[a]acridine.

abstract：:We report the results of a three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (PGK) with aryl and alkyl bisphosphonates. For the human enzyme, the IC50 values are predicted within a factor of 2 ove...

journal_title：Journal of medicinal chemistry

authors： Kotsikorou E,Sahota G,Oldfield E

更新日期：2006-11-16 00:00:00

abstract：:Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescr...

journal_title：Journal of medicinal chemistry

authors： Raymer B,Bhattacharya SK

更新日期：2018-12-13 00:00:00

abstract：:The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyzes the transfer of ADP-ribose units onto substrate proteins by using nicotinamide adenine dinucleotide (NAD(+)) as a cosubstrate. They have a documented role in chromatin remodelling and DNA repair, and inhibitors of ARTD1 and 2...

journal_title：Journal of medicinal chemistry

authors： Andersson CD,Karlberg T,Ekblad T,Lindgren AE,Thorsell AG,Spjut S,Uciechowska U,Niemiec MS,Wittung-Stafshede P,Weigelt J,Elofsson M,Schüler H,Linusson A

更新日期：2012-09-13 00:00:00

abstract：:N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing act...

journal_title：Journal of medicinal chemistry

authors： Kagechika H,Himi T,Kawachi E,Shudo K

更新日期：1989-10-01 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...

journal_title：Journal of medicinal chemistry

authors： Wright GE,Gambino JJ

更新日期：1984-02-01 00:00:00

abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

journal_title：Journal of medicinal chemistry

authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

更新日期：1997-10-10 00:00:00

abstract：:A series of regioisomeric substituted 6-O-benzyl ethers of 6 beta-naltrexol (12) in which isothiocyanate groups were attached directly to or one carbon removed from the aromatic ring of the benzyl group were prepared. These agents were prepared to obtain electrophilic opioid ligands potentially useful in the character...

journal_title：Journal of medicinal chemistry

authors： Davis RD,Nelson WL

更新日期：1995-02-03 00:00:00

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 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

abstract：:The development of a novel class of nonsteroidal human progesterone receptor (hPR) agonists, 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines 2, is described. The introduction of a 5-aryl group into the 1,2-dihydrocoumarino[3,4-f]quinoline core 1 is the key for progestational activities. The structure-activity relation...

journal_title：Journal of medicinal chemistry

authors： Zhi L,Tegley CM,Kallel EA,Marschke KB,Mais DE,Gottardis MM,Jones TK

更新日期：1998-01-29 00:00:00

abstract：:It is well established that intramolecular hydrogen bonding and N-methylation play important roles in the passive permeability of cyclic peptides, but other structural features have been explored less intensively. Recent studies on the oral bioavailability of the cyclic heptapeptide sanguinamide A have raised the ques...

journal_title：Journal of medicinal chemistry

authors： Bockus AT,Schwochert JA,Pye CR,Townsend CE,Sok V,Bednarek MA,Lokey RS

更新日期：2015-09-24 00:00:00

abstract：:The accessible surface, described by Lee and Richards (the L&R surface: J. Mol. Biol. 1971, 55, 379), has remarkably useful properties for displaying ligand-protein interactions. The surface is placed one van der Waals radius plus one probe radius away from the protein atoms. The ligands are displayed in skeletal form...

journal_title：Journal of medicinal chemistry

authors： Bohacek RS,McMartin C

更新日期：1992-05-15 00:00:00

abstract：:A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the opt...

journal_title：Journal of medicinal chemistry

authors： Zhang N,Zhang X,Zhu J,Turpoff A,Chen G,Morrill C,Huang S,Lennox W,Kakarla R,Liu R,Li C,Ren H,Almstead N,Venkatraman S,Njoroge FG,Gu Z,Clausen V,Graci J,Jung SP,Zheng Y,Colacino JM,Lahser F,Sheedy J,Mollin A

更新日期：2014-03-13 00:00:00

abstract：:The ortho hydroxy/methyl, hydroxy/hydroxymethyl, hydroxy/formyl, and hydroxy/carboxy substitution patterns, some of which confer dopaminergic agonist effects upon 2-aminotetralin ring systems, have been incorporated into beta-phenethylamine, 2-aminoindan, and trans-octahydrobenzo[f]quinoline rings. Certain of the 2-am...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Furlano DC,Dushin RG,Chang YA,Baird SR,Soliman LN,Flynn JR,Long JP,Bhatnagar RK

更新日期：1986-10-01 00:00:00

abstract：:A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37...

journal_title：Journal of medicinal chemistry

authors： Martinek TA,Otvös F,Dervarics M,Tóth G,Fülöp F

更新日期：2005-05-05 00:00:00

abstract：:In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular ...

journal_title：Journal of medicinal chemistry

authors： Thaker HD,Sgolastra F,Clements D,Scott RW,Tew GN

更新日期：2011-04-14 00:00:00

abstract：:A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of represen...

journal_title：Journal of medicinal chemistry

authors： Nandurkar NS,Zhang J,Ye Q,Ponomareva LV,She QB,Thorson JS

更新日期：2014-09-11 00:00:00

abstract：:Current drugs for the treatment of seizure disorders, although effective in many patients, still suffer from a number of failures and are not effective in some forms of resistant epilepsies. Historically, many of these drugs have multiple mechanisms of action including calcium and sodium channel blockade as well as GA...

journal_title：Journal of medicinal chemistry

authors： Fritch PC,McNaughton-Smith G,Amato GS,Burns JF,Eargle CW,Roeloffs R,Harrison W,Jones L,Wickenden AD

更新日期：2010-01-28 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：:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Baguley BC

更新日期：1984-03-01 00:00:00

abstract：:High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent tha...

journal_title：Journal of medicinal chemistry

authors： Duplantier AJ,Andresen CJ,Cheng JB,Cohan VL,Decker C,DiCapua FM,Kraus KG,Johnson KL,Turner CR,UmLand JP,Watson JW,Wester RT,Williams AS,Williams JA

更新日期：1998-06-18 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Dajani EZ,Pappo R,Gasiecki AF,Bianchi RG,Woods EM

更新日期：1983-06-01 00:00:00

abstract：:Human immunodeficiency virus (HIV) infection is now pandemic. Targeting HIV-1 reverse transcriptase (HIV-1 RT) has been considered as one of the most successful targets for the development of anti-HIV treatment. Among the HIV-1 RT inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) have gained a defin...

journal_title：Journal of medicinal chemistry

authors： Namasivayam V,Vanangamudi M,Kramer VG,Kurup S,Zhan P,Liu X,Kongsted J,Byrareddy SN

更新日期：2019-05-23 00:00:00

abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...

journal_title：Journal of medicinal chemistry

authors： Weet JF,Lenz GR

更新日期：1985-02-01 00:00:00

abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...

journal_title：Journal of medicinal chemistry

authors： Burke TG,Mi Z

更新日期：1994-01-07 00:00:00

abstract：:A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...

journal_title：Journal of medicinal chemistry

authors： Li H,Xie C,Lan R,Zha S,Chan CF,Wong WY,Ho KL,Chan BD,Luo Y,Zhang JX,Law GL,Tai WCS,Bünzli JG,Wong KL

更新日期：2017-11-09 00:00:00

abstract：:The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-la...

journal_title：Journal of medicinal chemistry

authors： Sam KM,Auger S,Luu-The V,Poirier D

更新日期：1995-10-27 00:00:00

abstract：:The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and ...

journal_title：Journal of medicinal chemistry

authors： Raitio KH,Savinainen JR,Vepsäläinen J,Laitinen JT,Poso A,Järvinen T,Nevalainen T

更新日期：2006-03-23 00:00:00

abstract：:A series of 2-(2-nitrobenzoyl)cyclohexane-1,3-dione analogues (1-9) were designed, synthesized, and evaluated for inhibition of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD), a key enzyme involved in the catabolism of tyrosine which catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. The correlations ...

journal_title：Journal of medicinal chemistry

authors： Wu CS,Huang JL,Sun YS,Yang DY

更新日期：2002-05-23 00:00:00