Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors: synthesis and evaluation of anti-reverse transcriptase activity of amide and ester analogues of lavendamycin.

abstract：:HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% o...

journal_title：Journal of medicinal chemistry

authors： Castro E,Martinez ZS,Seong CS,Cabrera-Espinoza A,Ruiz M,Hernandez Garcia A,Valdez F,Llano M,Echegoyen L

更新日期：2016-12-22 00:00:00

abstract：:C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of...

journal_title：Journal of medicinal chemistry

authors： Zhao H,Serby MD,Xin Z,Szczepankiewicz BG,Liu M,Kosogof C,Liu B,Nelson LT,Johnson EF,Wang S,Pederson T,Gum RJ,Clampit JE,Haasch DL,Abad-Zapatero C,Fry EH,Rondinone C,Trevillyan JM,Sham HL,Liu G

更新日期：2006-07-27 00:00:00

abstract：:A computational methodology is introduced to systematically organize compound analogue series according to substitution sites and identify combinations of sites that determine structure-activity relationships (SARs) and make large contributions to SAR discontinuity. These sites are prime targets for further chemical m...

journal_title：Journal of medicinal chemistry

authors： Peltason L,Weskamp N,Teckentrup A,Bajorath J

更新日期：2009-05-28 00:00:00

abstract：:Human thymidylate synthase (hTS), a target for antiproliferative drugs, is an obligate homodimer. Single-point mutations to alanine at the monomer-monomer interface may enable the identification of specific residues that delineate sites for drugs aimed at perturbing the protein-protein interactions critical for activi...

journal_title：Journal of medicinal chemistry

authors： Salo-Ahen OM,Tochowicz A,Pozzi C,Cardinale D,Ferrari S,Boum Y,Mangani S,Stroud RM,Saxena P,Myllykallio H,Costi MP,Ponterini G,Wade RC

更新日期：2015-04-23 00:00:00

abstract：:Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or ary...

journal_title：Journal of medicinal chemistry

authors： von Geldern TW,Kester JA,Bal R,Wu-Wong JR,Chiou W,Dixon DB,Opgenorth TJ

更新日期：1996-02-16 00:00:00

abstract：:New 2-piperazinylbenzothiazole and 2-piperazinylbenzoxazole derivatives were prepared and tested as 5-HT3 receptor antagonists. Some of the new compounds antagonized the effect of 5-HT at the longitudinal muscle myenteric plexus (LMMP) preparation of the guinea pig ileum, and two benzothiazole derivatives, compounds 2...

journal_title：Journal of medicinal chemistry

authors： Monge A,Peña MC,Palop JA,Calderó JM,Roca J,García E,Romero G,del Río J,Lasheras B

更新日期：1994-04-29 00:00:00

abstract：:1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivative...

journal_title：Journal of medicinal chemistry

authors： de las Heras FG,Alonso R,Alonso G

更新日期：1979-05-01 00:00:00

abstract：:We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterifi...

journal_title：Journal of medicinal chemistry

authors： McGuigan C,Madela K,Aljarah M,Bourdin C,Arrica M,Barrett E,Jones S,Kolykhalov A,Bleiman B,Bryant KD,Ganguly B,Gorovits E,Henson G,Hunley D,Hutchins J,Muhammad J,Obikhod A,Patti J,Walters CR,Wang J,Vernachio J,Ra

更新日期：2011-12-22 00:00:00

abstract：:We here report the synthesis of compounds structurally related to the high-affinity dopamine D(3) receptor ligand N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (1). All compounds were specifically designed as potential PET radioligands for brain D(3) receptors visualization, havin...

journal_title：Journal of medicinal chemistry

authors： Leopoldo M,Lacivita E,De Giorgio P,Colabufo NA,Niso M,Berardi F,Perrone R

更新日期：2006-01-12 00:00:00

abstract：:The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...

journal_title：Journal of medicinal chemistry

authors： Martin MW,Newcomb J,Nunes JJ,McGowan DC,Armistead DM,Boucher C,Buchanan JL,Buckner W,Chai L,Elbaum D,Epstein LF,Faust T,Flynn S,Gallant P,Gore A,Gu Y,Hsieh F,Huang X,Lee JH,Metz D,Middleton S,Mohn D,Morgenster

更新日期：2006-08-10 00:00:00

abstract：:5'-(Bromoacetamido)-2',5'-dideoxyuridine (3) and derivatives (8, 10, 12, and 14) substituted at the 5-position with bromo, iodo, fluoro, and ethyl groups have been synthesized as potential inhibitors of enzymes that metabolize pyrimidine nucleosides. Also prepared were 2',5'-dideoxyuridine derivatives (4-6) substitute...

journal_title：Journal of medicinal chemistry

authors： Elliott RD,Pruett PS,Brockman RW,Montgomery JA

更新日期：1987-05-01 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：: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：:Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands ...

journal_title：Journal of medicinal chemistry

authors： Cami-Kobeci G,Neal AP,Bradbury FA,Purington LC,Aceto MD,Harris LS,Lewis JW,Traynor JR,Husbands SM

更新日期：2009-03-26 00:00:00

abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Shirota FN

更新日期：1975-08-01 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 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 synthesis of 5-heteroaryl-substituted 2'-deoxyuridines is described. The heteroaromatics were obtained from three different 5-substituted 2'-deoxyuridines. Cycloaddition reaction of nitrile oxides on the 5-ethynyl derivative 1 gave the isoxazoles 4a-e. The thiazole derivatives 14a-c were obtained from the 5-thioca...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Snoeck R,Claes P,De Clercq E,Herdewijn P

更新日期：1991-06-01 00:00:00

abstract：:EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, the EGFR T790M secondary mutation has become a leading cause of clinically acquired resistance to these agents. Herein, on the basis of the previously reported irreversible EGFR i...

journal_title：Journal of medicinal chemistry

authors： Hao Y,Wang X,Zhang T,Sun D,Tong Y,Xu Y,Chen H,Tong L,Zhu L,Zhao Z,Chen Z,Ding J,Xie H,Xu Y,Li H

更新日期：2016-08-11 00:00:00

abstract：:Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...

journal_title：Journal of medicinal chemistry

authors： Tsen C,Iltis M,Kaur N,Bayer C,Delcros JG,von Kalm L,Phanstiel O 4th

更新日期：2008-01-24 00:00:00

abstract：:A series of 4'-substituted phenyl-4-piperidinylmethanol and benzoyl-4-piperidine derivatives was synthesized as potential novel serotonin 5-HT2A receptor ligands that can be radiolabeled for in vivo brain imaging. Compounds were prepared by alkylation of 4-substituted benzoyl-4-piperidine with an iodo- or fluoro-subst...

journal_title：Journal of medicinal chemistry

authors： Fu X,Tan PZ,Kula NS,Baldessarini R,Tamagnan G,Innis RB,Baldwin RM

更新日期：2002-05-23 00:00:00

abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...

journal_title：Journal of medicinal chemistry

authors： López-Rodríguez ML,Viso A,Ortega-Gutiérrez S,Lastres-Becker I,González S,Fernández-Ruiz J,Ramos JA

更新日期：2001-12-20 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：:The stereospecific synthesis of several 4-[(4-carboxyphenyl)oxy]- 3,3-dialkyl-1-[[(1-phenylalkyl)-amino]carbonyl]azetidin-2-on es 3 is described in which the C-3 alkyl groups were varied from methyl to butyl as well as allyl, benzyl and methoxymethyl. The structure-activity relations for these compounds are discussed ...

journal_title：Journal of medicinal chemistry

authors： Finke PE,Shah SK,Fletcher DS,Ashe BM,Brause KA,Chandler GO,Dellea PS,Hand KM,Maycock AL,Osinga DG

更新日期：1995-06-23 00:00:00

abstract：:Continuing structure-activity studies on the anticonvulsant activity of analogs of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (2a), which displayed anti-electroshock seizure (MES) activity and a protective index (TD50/ED50) of > 4.5 are reported. An in-depth analysis of this moiety was studied employing the Topliss...

journal_title：Journal of medicinal chemistry

authors： Farrar VA,Ciechanowicz-Rutkowska M,Grochowski J,Serda P,Pilati T,Filippini G,Hinko CN,el-Assadi A,Moore JA,Edafiogho IO

更新日期：1993-11-12 00:00:00

abstract：:The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature me...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Gangjee A

更新日期：1976-07-01 00:00:00

abstract：:New imidazo[1,2-a]pyridines substituted at the 3-position have been synthesized as potential antisecretory and cytoprotective antiulcer agents. The synthetic routes began with cyclization of aminopyridines 5a,b and chloro ketones 6a,b to give imidazo[1,2-a]pyridines 7-9. The side chain at the 3-position was elaborated...

journal_title：Journal of medicinal chemistry

authors： Starrett JE Jr,Montzka TA,Crosswell AR,Cavanagh RL

更新日期：1989-09-01 00:00:00

abstract：:The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure-activity...

journal_title：Journal of medicinal chemistry

authors： Macsari I,Besidski Y,Csjernyik G,Nilsson LI,Sandberg L,Yngve U,Ahlin K,Bueters T,Eriksson AB,Lund PE,Venyike E,Oerther S,Hygge Blakeman K,Luo L,Arvidsson PI

更新日期：2012-08-09 00:00:00

abstract：:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake i...

journal_title：Journal of medicinal chemistry

authors： Monaco I,Camorani S,Colecchia D,Locatelli E,Calandro P,Oudin A,Niclou S,Arra C,Chiariello M,Cerchia L,Comes Franchini M

更新日期：2017-05-25 00:00:00

abstract：:A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, a...

journal_title：Journal of medicinal chemistry

authors： Shang R,Pu X,Xu X,Xin Z,Zhang C,Guo W,Liu Y,Liang J

更新日期：2014-07-10 00:00:00