Antimalarials. Synthesis and antimalarial activity of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine and derivatives.

abstract：:A number of 2-oxoquinoline-1-alkanoic acids that contain the N-acylglycine fragment found in several known inhibitors of aldose reductase were synthesized and tested in the rat lens assay. All of the target compounds were prepared by alkylation of the appropriate 2-oxoquinoline intermediates with a halo ester, followe...

journal_title：Journal of medicinal chemistry

authors： DeRuiter J,Brubaker AN,Whitmer WL,Stein JL Jr

更新日期：1986-10-01 00:00:00

abstract：:Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (P...

journal_title：Journal of medicinal chemistry

authors： Soliman W,Wang L,Bhattacharjee S,Kaur K

更新日期：2011-04-14 00:00:00

abstract：:Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by...

journal_title：Journal of medicinal chemistry

authors： Conradi RA,Vander Wyk JC,Bowlus SB

更新日期：1979-08-01 00:00:00

abstract：:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a po...

journal_title：Journal of medicinal chemistry

authors： Xu J,Cole DC,Chang CP,Ayyad R,Asselin M,Hao W,Gibbons J,Jelinsky SA,Saraf KA,Park K

更新日期：2008-07-24 00:00:00

abstract：:Three novel C-4 aziridine-bearing paclitaxel analogs, 3-5, have been synthesized during the course of our continuing effort at C-4 modification. The key step in the synthesis is the aziridine ring formation at the C-4 position via an intramolecular Mitsunobu reaction. The syntheses and the biological evaluation of the...

journal_title：Journal of medicinal chemistry

authors： Chen SH,Fairchild C,Long BH

更新日期：1995-06-09 00:00:00

abstract：:New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...

journal_title：Journal of medicinal chemistry

authors： Miranda MT,Liddle RA,Rivier JE

更新日期：1993-06-11 00:00:00

abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...

journal_title：Journal of medicinal chemistry

authors： Singh JP,Tamang S,Rajamohanan PR,Jima NC,Chakraborty G,Kundu GC,Gaikwad SM,Khan MI

更新日期：2010-07-22 00:00:00

abstract：:Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs...

journal_title：Journal of medicinal chemistry

authors： Hagen H,Marzenell P,Jentzsch E,Wenz F,Veldwijk MR,Mokhir A

更新日期：2012-01-26 00:00:00

abstract：:Enantiostructure-activity studies of chlorophenoxybutyric and propionic acids have provided evidence for the dissociation of serum cholesterol lowering and platelet antiaggregatory activities from the adverse chloride ion channel mediated myotonic effects of these compounds. R-(+) propionic and butyric acid enantiomer...

journal_title：Journal of medicinal chemistry

authors： Feller DR,Kamanna VS,Newman HA,Romstedt KJ,Witiak DT,Bettoni G,Bryant SH,Conte-Camerino D,Loiodice F,Tortorella V

更新日期：1987-08-01 00:00:00

abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

更新日期：1981-01-01 00:00:00

abstract：:A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)eth...

journal_title：Journal of medicinal chemistry

authors： McCall JM,McCall RB,TenBrink RE,Kamdar BV,Humphrey SJ,Sethy VH,Harris DW,Daenzer C

更新日期：1982-01-01 00:00:00

abstract：:The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed. The approach was successful for the cases considered and suggests that this may be useful for the design of inhibitors in the lead optimization...

journal_title：Journal of medicinal chemistry

authors： Lyne PD,Lamb ML,Saeh JC

更新日期：2006-08-10 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Seven 3-alkyl-4-aryl-1,5-dihydro-2H-pyrrol-2-ones were prepared as potential inhibitors of cardiac cAMP phosphodiesterase (PDE). The design of these compounds made use of rolipram, a known inhibitor of the brain cAMP PDE isozyme, as a lead structure and was guided by a model which describes the features required for p...

journal_title：Journal of medicinal chemistry

authors： Lampe JW,Chou YL,Hanna RG,Di Meo SV,Erhardt PW,Hagedorn AA 3rd,Ingebretsen WR,Cantor E

更新日期：1993-04-16 00:00:00

abstract：:Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminometh...

journal_title：Journal of medicinal chemistry

authors： Kung HF,Newman S,Choi SR,Oya S,Hou C,Zhuang ZP,Acton PD,Plössl K,Winkler J,Kung MP

更新日期：2004-10-07 00:00:00

abstract：:Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Murray J,Lai KW,Tsui V,Albrecht BK,An L,Beresini MH,de Leon Boenig G,Bronner SM,Chan EW,Chen KX,Chen Z,Choo EF,Clagg K,Clark K,Crawford TD,Cyr P,de Almeida Nagata D,Gascoigne KE,Grogan JL,Hatzivassiliou

更新日期：2017-11-22 00:00:00

abstract：:The discovery and structure-activity relationship of first-generation small-molecule malonyl-CoA decarboxylase (MCD; CoA = coenzyme A) inhibitors are reported. We demonstrated that MCD inhibitors increased malonyl-CoA concentration in the isolated working rat hearts. Malonyl-CoA is a potent, endogenous, and allosteric...

journal_title：Journal of medicinal chemistry

authors： Cheng JF,Chen M,Wallace D,Tith S,Haramura M,Liu B,Mak CC,Arrhenius T,Reily S,Brown S,Thorn V,Harmon C,Barr R,Dyck JR,Lopaschuk GD,Nadzan AM

更新日期：2006-03-09 00:00:00

abstract：:G protein-coupled receptors (GPCRs) belong to a large superfamily of membrane receptors mediating a variety of physiological functions. As such they are attractive targets for drug therapy. However, it remains a challenge to develop subtype selective GPCR ligands due to the high conservation of orthosteric binding sit...

journal_title：Journal of medicinal chemistry

authors： Fronik P,Gaiser BI,Sejer Pedersen D

更新日期：2017-05-25 00:00:00

abstract：:Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...

journal_title：Journal of medicinal chemistry

authors： Patel S,Cohen F,Dean BJ,De La Torre K,Deshmukh G,Estrada AA,Ghosh AS,Gibbons P,Gustafson A,Huestis MP,Le Pichon CE,Lin H,Liu W,Liu X,Liu Y,Ly CQ,Lyssikatos JP,Ma C,Scearce-Levie K,Shin YG,Solanoy H,Stark KL,Wa

更新日期：2015-01-08 00:00:00

abstract：:Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs lice...

journal_title：Journal of medicinal chemistry

authors： Geitmann M,Unge T,Danielson UH

更新日期：2006-04-20 00:00:00

abstract：:The synthesis and biological evaluation of a series of novel 1-(aryloxy)-2-propanolamines and several related deshydroxy analogues are described. Compounds 4-29 were prepared and investigated for their class III electrophysiological activity in isolated canine Purkinje fibers and in anesthetized open-chest dogs. None ...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Spinelli W,Anantharaman V,Marcopulos N,Parsons RW,Moubarak IF,Cullinan C,Bagli JF

更新日期：1991-11-01 00:00:00

abstract：:Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine se...

journal_title：Journal of medicinal chemistry

authors： Schenkel LB,Huang X,Cheng A,Deak HL,Doherty E,Emkey R,Gu Y,Gunaydin H,Kim JL,Lee J,Loberg R,Olivieri P,Pistillo J,Tang J,Wan Q,Wang HL,Wang SW,Wells MC,Wu B,Yu V,Liu L,Geuns-Meyer S

更新日期：2011-12-22 00:00:00

abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

更新日期：2008-12-11 00:00:00

abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

journal_title：Journal of medicinal chemistry

authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

更新日期：1977-02-01 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:Inhibition of growth hormone (GH) and prolactin (PRL) release from the anterior pituitary gland is mediated through somatostatin receptor subtypes sst2 and sst5. It has been found that somatostatin (SS) analogues that are selective for both receptor subtypes are more effective at inhibiting GH and PRL release than mon...

journal_title：Journal of medicinal chemistry

authors： Moore SB,van der Hoek J,de Capua A,van Koetsveld PM,Hofland LJ,Lamberts SW,Goodman M

更新日期：2005-10-20 00:00:00

abstract：:The solid-phase reductive alkylation of the Lys side chain in positions 6 (D) and 8 (L) and position 8 alone of the LH-RH antagonist [N-Ac-D-Nal,D-Ph2,3,D-Arg6,Phe7,D-Ala10]LH-RH was investigated in an attempt to reduce the histamine-releasing activity inherent to most potent antagonists while retaining high antiovula...

journal_title：Journal of medicinal chemistry

authors： Hocart SJ,Nekola MV,Coy DH

更新日期：1987-10-01 00:00:00

abstract：:The structure of azaprophen, which was originally assigned by 1H NMR analysis, was confirmed by X-ray crystallography. A comparison of 13C NMR isotropic chemical shift data for azaprophen in the solid state and in CDCl3 and DMSO-d6 solution was used to correlate solution and solid-state conformation as determined by t...

journal_title：Journal of medicinal chemistry

authors： Carroll FI,Abraham P,Mascarella SW,Singh P,Moreland CG,Sankar SS,Kwon YW,Triggle DJ

更新日期：1991-04-01 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：:A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clini...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Krushinski JH,Beedle EE,Leander JD,Wong DT,Rathbun RC

更新日期：1986-09-01 00:00:00