Development of a structural model for NF-kappaB inhibition of sesquiterpene lactones using self-organizing neural networks.

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：: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：:The synthesis and biological activities of a series of N-substituted cis-4a,5,6,7,8,8a-hexa- and cis-4a,5,8,8a-tetrahydro-2H-phthalazin-1-ones are described. It was found that compounds bearing a cycloalkyl group at the 2-position exhibit the highest PDE4 inhibitory activities (pIC(50) = 8.6-9.4). The N-cycloheptyl- a...

journal_title：Journal of medicinal chemistry

authors： Van der Mey M,Boss H,Hatzelmann A,Van der Laan IJ,Sterk GJ,Timmerman H

更新日期：2002-06-06 00:00:00

abstract：:The prevalence of neurotensin receptor (NTR) in several human tumors makes it an attractive target for the delivery of cytotoxic drugs and imaging agents. Native neurotensin (NT) is a tridecapeptide that binds to NTR and induces tumor growth. Unfortunately, NT has a short plasma half-life, which hinders its use for in...

journal_title：Journal of medicinal chemistry

authors： Achilefu S,Srinivasan A,Schmidt MA,Jimenez HN,Bugaj JE,Erion JL

更新日期：2003-07-17 00:00:00

abstract：:Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route inv...

journal_title：Journal of medicinal chemistry

authors： Chaudhary V,Venghateri JB,Dhaked HP,Bhoyar AS,Guchhait SK,Panda D

更新日期：2016-04-14 00:00:00

abstract：:N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a-g can exist in conformations w...

journal_title：Journal of medicinal chemistry

authors： Carroll FI,Chaudhari S,Thomas JB,Mascarella SW,Gigstad KM,Deschamps J,Navarro HA

更新日期：2005-12-29 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：:A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulf...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Xu SP,Zhu LY,Cosby LA,Sartorelli AC

更新日期：1989-07-01 00:00:00

abstract：:A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalo...

journal_title：Journal of medicinal chemistry

authors： Jia X,Yang FF,Li J,Liu JY,Xue JP

更新日期：2013-07-25 00:00:00

abstract：:A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration proces...

journal_title：Journal of medicinal chemistry

authors： Pasquini S,Mugnaini C,Tintori C,Botta M,Trejos A,Arvela RK,Larhed M,Witvrouw M,Michiels M,Christ F,Debyser Z,Corelli F

更新日期：2008-08-28 00:00:00

abstract：:Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene ...

journal_title：Journal of medicinal chemistry

authors： Meng G,Pu J,Li Y,Han A,Tian Y,Xu W,Zhang T,Li X,Lu L,Wang C,Jiang S,Liu K

更新日期：2019-10-10 00:00:00

abstract：:Synthesis of four arabinofuranosyl derivatives of the antitumor agent 3-deazaguanine is described. By the use of 13C and 1H nuclear magnetic resonance spectroscopy, the structures of these nucleosides were established to be alpha and beta pairs of N-7 and N-9 arabinosides of 3-deazaguanine. In contrast to 3-deazaguani...

journal_title：Journal of medicinal chemistry

authors： Poonian MS,McComas WW,Kramer MJ

更新日期：1979-08-01 00:00:00

abstract：:Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds, including an AZT analogue, show modest antivirial activity against HIV-1 and HIV-2 r...

journal_title：Journal of medicinal chemistry

authors： Okruszek A,Olesiak M,Balzarini J

更新日期：1994-10-28 00:00:00

abstract：:A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of the novel amidinoindole and benzofuran compounds, I and II. Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 29, which displayed an IC50 value o...

journal_title：Journal of medicinal chemistry

authors： Su T,Naughton MA,Smyth MS,Rose JW,Arfsten AE,McCowan JR,Jakubowski JA,Wyss VL,Ruterbories KJ,Sall DJ,Scarborough RM

更新日期：1997-12-19 00:00:00

abstract：:On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2',3'-dideoxy-2',3'-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxyg...

journal_title：Journal of medicinal chemistry

authors： Jeong LS,Kim HO,Moon HR,Hong JH,Yoo SJ,Choi WJ,Chun MW,Lee CK

更新日期：2001-03-01 00:00:00

abstract：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Omnaas JR,Lomize A,Heyl DL,Nordan I,Mousigian C,Davis P,Porreca F

更新日期：1994-12-09 00:00:00

abstract：:The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopu...

journal_title：Journal of medicinal chemistry

authors： Spletstoser JT,Flaherty PT,Himes RH,Georg GI

更新日期：2004-12-16 00:00:00

abstract：:A series of cis and trans bicyclic lactones was prepared as congeners of podophyllotoxin (1) and evaluated as antimitotic agents both in cell cultures grown in vitro and in an in vitro protein binding assay. All compounds displayed insignificant activity-a result which may reflect insufficient structural similarity to...

journal_title：Journal of medicinal chemistry

authors： Smissman EE,Murray RJ,McChesney JD,Houston LL,Pazdernik TL

更新日期：1976-01-01 00:00:00

abstract：:5'-Deoxy-5-fluorouridine (5'-dFUrd, 1) possesses a significantly higher chemotherapeutic index than other fluoropyrimidines as a result of its being selectivity cleaved in tumors to 5-fluorouracil (FUra) by uridine phosphorylase. Because 1 is a relatively poor substrate for this enzyme, we synthesized a series of 5'-d...

journal_title：Journal of medicinal chemistry

authors： Ajmera S,Danenberg PV

更新日期：1982-08-01 00:00:00

abstract：:The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure predictio...

journal_title：Journal of medicinal chemistry

authors： Patargias G,Zitzmann N,Dwek R,Fischer WB

更新日期：2006-01-26 00:00:00

abstract：:K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ intera...

journal_title：Journal of medicinal chemistry

authors： Zimmermann G,Schultz-Fademrecht C,Küchler P,Murarka S,Ismail S,Triola G,Nussbaumer P,Wittinghofer A,Waldmann H

更新日期：2014-06-26 00:00:00

abstract：:N-(R)- and N-(S)-lactylsphingosine and their corresponding dihydrosphingosine derivatives were synthesized. The antileukemic activities of these compounds were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in human leukemia HL-60 cells. N-(R)- and N-(S)-Lactylsphingosine disp...

journal_title：Journal of medicinal chemistry

authors： Azuma H,Takao R,Shikata K,Niiro H,Tachibana T,Ogino K

更新日期：2003-07-31 00:00:00

abstract：:A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor subtypes. The data indicated that a considerable degree of structural variati...

journal_title：Journal of medicinal chemistry

authors： de Costa BR,He XS,Dominguez C,Cutts J,Williams W,Bowen WD

更新日期：1994-01-21 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 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：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...

journal_title：Journal of medicinal chemistry

authors： Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

更新日期：2011-07-28 00:00:00

abstract：:Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...

journal_title：Journal of medicinal chemistry

authors： Sham HL,Bolis G,Stein HH,Fesik SW,Marcotte PA,Plattner JJ,Rempel CA,Greer J

更新日期：1988-02-01 00:00:00

abstract：:Identifying local similarities in binding sites from distant proteins is a major hurdle to rational drug design. We herewith present a novel method, borrowed from computer vision, adapted to mine fragment subpockets and compare them to whole ligand-binding sites. Pockets are represented by pharmacophore-annotated poin...

journal_title：Journal of medicinal chemistry

authors： Eguida M,Rognan D

更新日期：2020-07-09 00:00:00

abstract：:Fifteen anthracene-9,10-dione ("anthraquinone") derivatives with (omega-aminoalkyl)carboxamido substituents at the 1-, 2-, 1,4-, or 2, 6-ring positions were tested for bacterial mutagenicity in reverse-mutation assays using Salmonella typhimurium frameshift strains TA1538, TA98, and TA97a, in the presence and absence ...

journal_title：Journal of medicinal chemistry

authors： Venitt S,Crofton-Sleigh C,Agbandje M,Jenkins TC,Neidle S

更新日期：1998-09-10 00:00:00

abstract：:The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human p...

journal_title：Journal of medicinal chemistry

authors： Williams LK,Li C,Withers SG,Brayer GD

更新日期：2012-11-26 00:00:00