Structure-activity relationships of the antimalarial agent artemisinin. 2. Effect of heteroatom substitution at O-11: synthesis and bioassay of N-alkyl-11-aza-9-desmethylartemisinins.

abstract：:A series of 59 alpha-aryl-alpha-thioether-alkyl, -alkanenitrile, and -alkanecarboxylic acid methyl ester tetrahydroisoquinoline and isoindoline derivatives (15a-48) were synthesized and evaluated as multidrug resistance (MDR) reversal agents. The compounds were tested on S1-B1-20 human colon carcinoma cells selected f...

journal_title：Journal of medicinal chemistry

authors： Berger D,Citarella R,Dutia M,Greenberger L,Hallett W,Paul R,Powell D

更新日期：1999-06-17 00:00:00

abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

journal_title：Journal of medicinal chemistry

authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

更新日期：1981-05-01 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：:On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an...

journal_title：Journal of medicinal chemistry

authors： Surleraux DL,de Kock HA,Verschueren WG,Pille GM,Maes LJ,Peeters A,Vendeville S,De Meyer S,Azijn H,Pauwels R,de Bethune MP,King NM,Prabu-Jeyabalan M,Schiffer CA,Wigerinck PB

更新日期：2005-03-24 00:00:00

abstract：:A new class of potential antitumor agents inspired by the enediyne antitumor antibiotics has been synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of re...

journal_title：Journal of medicinal chemistry

authors： Laroche C,Li J,Kerwin SM

更新日期：2011-07-28 00:00:00

abstract：:Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and poten...

journal_title：Journal of medicinal chemistry

authors： Thorat SA,Lee Y,Jung A,Ann J,Ahn S,Baek J,Zuo D,Do N,Jeong JJ,Blumberg PM,Esch TE,Turcios NA,Pearce LV,Ha HJ,Yoo YD,Hong S,Choi S,Lee J

更新日期：2021-01-14 00:00:00

abstract：:As a receptor tyrosine kinase of insulin receptor (IR) subfamily, anaplastic lymphoma kinase (ALK) has been validated to play important roles in various cancers, especially anaplastic large cell lymphoma (ALCL), nonsmall cell lung cancer (NSCLC), and neuroblastomas. Currently, five small-molecule inhibitors of ALK, in...

journal_title：Journal of medicinal chemistry

authors： Kong X,Pan P,Sun H,Xia H,Wang X,Li Y,Hou T

更新日期：2019-12-26 00:00:00

abstract：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...

journal_title：Journal of medicinal chemistry

authors： Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske J

更新日期：2018-02-22 00:00:00

abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...

journal_title：Journal of medicinal chemistry

authors： Smith PA,Sorich MJ,McKinnon RA,Miners JO

更新日期：2003-04-24 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：:The malignant brain tumor (MBT) repeat is an important epigenetic-code "reader" and is functionally associated with differentiation, gene silencing, and tumor suppression. (1-3) Small molecule probes of MBT domains should enable a systematic study of MBT-containing proteins and potentially reveal novel druggable targe...

journal_title：Journal of medicinal chemistry

authors： Kireev D,Wigle TJ,Norris-Drouin J,Herold JM,Janzen WP,Frye SV

更新日期：2010-11-11 00:00:00

abstract：:alpha-Ethynyl- and alpha-vinylornithine were designed and synthesized as potential enzyme-activated inhibitors of mammalian ornithine decarboxylase. These two new inhibitors produce both immediate and time-dependent inhibition of rat liver ornithine decarboxylase in vitro. The inhibitions exhibition saturation kinetic...

journal_title：Journal of medicinal chemistry

authors： Danzin C,Casara P,Claverie N,Metcalf BW

更新日期：1981-01-01 00:00:00

abstract：:The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was obse...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung HF,Billings J,Guo YZ,Wu Y,Shih J

更新日期：1989-03-01 00:00:00

abstract：:Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of caveolin-1 oligomers. Developed and optimized through screening and analysis of synthetic peptide libraries, ligand 1 has 75...

journal_title：Journal of medicinal chemistry

authors： Gilliam AJ,Smith JN,Flather D,Johnston KM,Gansmiller AM,Fishman DA,Edgar JM,Balk M,Majumdar S,Weiss GA

更新日期：2016-04-28 00:00:00

abstract：:Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be ...

journal_title：Journal of medicinal chemistry

authors： Ai T,Xu Y,Qiu L,Geraghty RJ,Chen L

更新日期：2015-01-22 00:00:00

abstract：:1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to a...

journal_title：Journal of medicinal chemistry

authors： Mohamadi F,Spees MM,Staten GS,Marder P,Kipka JK,Johnson DA,Boger DL,Zarrinmayeh H

更新日期：1994-01-21 00:00:00

abstract：:It is a great challenge to develop drugs for treatment of metabolic syndrome. With ganomycin I as a leading compound, 14 meroterpene derivatives were synthesized and screened for their α-glucosidase and HMG-CoA reductase inhibitory activities. As a result, a α-glucosidase and HMG-CoA reductase dual inhibitor (( R, E)-...

journal_title：Journal of medicinal chemistry

authors： Wang K,Bao L,Zhou N,Zhang J,Liao M,Zheng Z,Wang Y,Liu C,Wang J,Wang L,Wang W,Liu S,Liu H

更新日期：2018-04-26 00:00:00

abstract：:Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this se...

journal_title：Journal of medicinal chemistry

authors： Mao J,Yuan H,Wang Y,Wan B,Pieroni M,Huang Q,van Breemen RB,Kozikowski AP,Franzblau SG

更新日期：2009-11-26 00:00:00

abstract：:The design and synthesis of potent and selective neurokinin NK-2 receptor agonists 12 (GR64349) and 31 are described, together with structure-activity relationships for related analogues. Compound 12 (EC50 = 3.7 nM at NK-2 receptors in the rat colon; selectivity > 1000- and > 300-fold with respect to NK-1 and NK-3 rec...

journal_title：Journal of medicinal chemistry

authors： Deal MJ,Hagan RM,Ireland SJ,Jordan CC,McElroy AB,Porter B,Ross BC,Stephens-Smith M,Ward P

更新日期：1992-10-30 00:00:00

abstract：:The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it ...

journal_title：Journal of medicinal chemistry

authors： Russell MG,Carling RW,Street LJ,Hallett DJ,Goodacre S,Mezzogori E,Reader M,Cook SM,Bromidge FA,Newman R,Smith AJ,Wafford KA,Marshall GR,Reynolds DS,Dias R,Ferris P,Stanley J,Lincoln R,Tye SJ,Sheppard WF,Sohal B,

更新日期：2006-02-23 00:00:00

abstract：:Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid dis...

journal_title：Journal of medicinal chemistry

authors： Wu J,Zhang Y,Maida LE,Santos RG,Welmaker GS,LaVoi TM,Nefzi A,Yu Y,Houghten RA,Toll L,Giulianotti MA

更新日期：2013-12-27 00:00:00

abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...

journal_title：Journal of medicinal chemistry

authors： Lin J,Deng H,Jin L,Pandey P,Quinn J,Cantin S,Rynkiewicz MJ,Gorga JC,Bibbins F,Celatka CA,Nagafuji P,Bannister TD,Meyers HV,Babine RE,Hayward NJ,Weaver D,Benjamin H,Stassen F,Abdel-Meguid SS,Strickler JE

更新日期：2006-12-28 00:00:00

abstract：:Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response. ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Ballard P,Bardelle C,Cockerill M,Colclough N,Critchlow SE,Debreczeni J,Fairley G,Fillery S,Graham MA,Goodwin L,Guichard S,Hudson K,Ward RA,Whittaker D

更新日期：2015-03-26 00:00:00

abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

journal_title：Journal of medicinal chemistry

authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

更新日期：1997-07-04 00:00:00

abstract：:A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-s...

journal_title：Journal of medicinal chemistry

authors： Elliott RL,Pireh D,Griesgraber G,Nilius AM,Ewing PJ,Bui MH,Raney PM,Flamm RK,Kim K,Henry RF,Chu DT,Plattner JJ,Or YS

更新日期：1998-05-07 00:00:00

abstract：:The binding and solution-phase properties of six inhibitors of FK506 binding protein (FKBP12) were investigated using free energy perturbation techniques in Monte Carlo statistical mechanics simulations. These nonimmunosuppressive molecules are of current interest for their neurotrophic activity when bound to FKBP12 a...

journal_title：Journal of medicinal chemistry

authors： Lamb ML,Jorgensen WL

更新日期：1998-10-08 00:00:00

abstract：:The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were test...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Fontana G,Bombardelli E,Tinelli S,Beretta GL,Basili S,Moro S,Zunino F,Battaglia A

更新日期：2009-02-26 00:00:00

abstract：:Resistant HCV variants carrying NS5B S282T mutation confer reduced sensitivity to sofosbuvir, the sole marketed NS5B polymerase inhibitor. On the basis of the finding that 2'-α-F-2'-β-C-methylcytidine 5'-triphosphate (8) was more potent than sofosbuvir's active metabolite on inhibition of both wild-type and S282T muta...

journal_title：Journal of medicinal chemistry

authors： Zhen L,Dai L,Wen X,Yao L,Jin X,Yang XW,Zhao W,Yu SQ,Yuan H,Wang G,Sun H

更新日期：2017-07-27 00:00:00

abstract：:The possibility that catecholamines can be oxidized via aberrant pathways in vivo is open to question, but in vitro oxidation via aerobic manipulations is established. Assuming oxidation does occur, we have examined quantitatively the fast chemical reactions of the initial oxidation products, the o-quinones. The natur...

journal_title：Journal of medicinal chemistry

authors： Tse DC,McCreery RL,Adams RN

更新日期：1976-01-01 00:00:00

abstract：:The sphingoid base derived class of lipids (sphingolipids) is a family of interconverting molecules that play key roles in numerous structural and signaling processes. The biosynthetic pathway of the sphingolipids affords many opportunities for therapeutic intervention: targeting the ligands directly, targeting the va...

journal_title：Journal of medicinal chemistry

authors： Dyckman AJ

更新日期：2017-07-13 00:00:00