Synthesis and potent antileukemic activities of N-lactylsphingosine and N-lactyldihydrosphingosine.

abstract：:The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows p...

journal_title：Journal of medicinal chemistry

authors： Ma D,Jiang Y,Chen F,Gong LK,Ding K,Xu Y,Wang R,Ge A,Ren J,Li J,Li J,Ye Q

更新日期：2006-01-26 00:00:00

abstract：:Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a m...

journal_title：Journal of medicinal chemistry

authors： Shimshoni JA,Bialer M,Wlodarczyk B,Finnell RH,Yagen B

更新日期：2007-12-13 00:00:00

abstract：:Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which afte...

journal_title：Journal of medicinal chemistry

authors： Boztaş M,Çetinkaya Y,Topal M,Gülçin İ,Menzek A,Şahin E,Tanc M,Supuran CT

更新日期：2015-01-22 00:00:00

abstract：:A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-im idazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a signif...

journal_title：Journal of medicinal chemistry

authors： Jarosinski MA,Reddy PS,Anderson WK

更新日期：1993-11-12 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：:The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relations...

journal_title：Journal of medicinal chemistry

authors： King PJ,Ma G,Miao W,Jia Q,McDougall BR,Reinecke MG,Cornell C,Kuan J,Kim TR,Robinson WE Jr

更新日期：1999-02-11 00:00:00

abstract：:The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity compa...

journal_title：Journal of medicinal chemistry

authors： Kanne DB,Abood LG

更新日期：1988-03-01 00:00:00

abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...

journal_title：Journal of medicinal chemistry

authors： van Vliet LA,Tepper PG,Dijkstra D,Damsma G,Wikström H,Pugsley TA,Akunne HC,Heffner TG,Glase SA,Wise LD

更新日期：1996-10-11 00:00:00

abstract：:A molecular model of the alpha3beta2 nAChR lumen channel was constructed and hydrophobic clefts were observed near the receptor gate. Docking simulations indicated that ligand-nAChR complexes were formed by hydrophobic interactions with the cleft and hydrogen bond interactions. The equilibrium constants and associatio...

journal_title：Journal of medicinal chemistry

authors： Jozwiak K,Ravichandran S,Collins JR,Moaddel R,Wainer IW

更新日期：2007-11-29 00:00:00

abstract：:The discovery of somatic Jak2 mutations in patients with chronic myeloproliferative neoplasms has led to significant interest in discovering selective Jak2 inhibitors for use in treating these disorders. A high-throughput screening effort identified the pyrazolo[1,5-a]pyrimidine scaffold as a potent inhibitor of Jak2....

journal_title：Journal of medicinal chemistry

authors： Hanan EJ,van Abbema A,Barrett K,Blair WS,Blaney J,Chang C,Eigenbrot C,Flynn S,Gibbons P,Hurley CA,Kenny JR,Kulagowski J,Lee L,Magnuson SR,Morris C,Murray J,Pastor RM,Rawson T,Siu M,Ultsch M,Zhou A,Sampath D,Ly

更新日期：2012-11-26 00:00:00

abstract：:Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against t...

journal_title：Journal of medicinal chemistry

authors： Gomez-Monterrey I,Campiglia P,Carotenuto A,Stiuso P,Bertamino A,Sala M,Aquino C,Grieco P,Morello S,Pinto A,Ianelli P,Novellino E

更新日期：2008-05-22 00:00:00

abstract：:We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-h...

journal_title：Journal of medicinal chemistry

authors： de Medina P,Paillasse MR,Payré B,Silvente-Poirot S,Poirot M

更新日期：2009-12-10 00:00:00

abstract：:A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

journal_title：Journal of medicinal chemistry

authors： Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

更新日期：1997-03-28 00:00:00

abstract：:The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...

journal_title：Journal of medicinal chemistry

authors： Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

更新日期：2020-10-08 00:00:00

abstract：:The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype...

journal_title：Journal of medicinal chemistry

authors： Kim YC,Ji XD,Jacobson KA

更新日期：1996-10-11 00:00:00

abstract：:Malaria represents a significant health issue, and novel and effective drugs are needed to address parasite resistance that has emerged to the current drug arsenal. Antimalarial drug discovery has historically benefited from a whole-cell (phenotypic) screening approach to identify lead molecules. This approach has bee...

journal_title：Journal of medicinal chemistry

authors： Chatterjee AK

更新日期：2013-10-24 00:00:00

abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...

journal_title：Journal of medicinal chemistry

authors： Doll MK,Nichols DE,Kilts JD,Prioleau C,Lawler CP,Lewis MM,Mailman RB

更新日期：1999-03-11 00:00:00

abstract：:Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycin...

journal_title：Journal of medicinal chemistry

authors： Elomri A,Mitaku S,Michel S,Skaltsounis AL,Tillequin F,Koch M,Pierré A,Guilbaud N,Léonce S,Kraus-Berthier L,Rolland Y,Atassi G

更新日期：1996-11-22 00:00:00

abstract：:An enzymatically activated liposome-based drug-delivery concept involving masked antitumor ether lipids (AELs) has been investigated. This concept takes advantage of the cytotoxic properties of AEL drugs as well as the membrane permeability enhancing properties of these molecules, which can lead to enhanced drug diffu...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Davidsen J,Begtrup M,Mouritsen OG,Jørgensen K

更新日期：2004-03-25 00:00:00

abstract：:Opical antipodes of the axial phenyl analgetic, alpha-promedol hydrochloride (3), were prepared and the absolute stereochemistry wasd determined by relating one of the enantiomers to its gamme diastereomer having the 2S, 4S,5R configuration. The analegetic potency of (+)-(2R,4S,5S)-3 is 20 times that of morphine, whil...

journal_title：Journal of medicinal chemistry

authors： Fries DF,Portoghese PS

更新日期：1976-09-01 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：:Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of he...

journal_title：Journal of medicinal chemistry

authors： Moon KY,Shirota FN,Baturay N,Kwon CH

更新日期：1995-03-03 00:00:00

abstract：:Naturally occurring N(ω)-hydroxy-l-arginine (NOHA, 1) is the best substrate of NO synthases (NOS). The development of stable and bioavailable prodrugs would provide a pharmacologically valuable strategy for the treatment of cardiovascular diseases that are associated with endothelial dysfunction. To improve NOHAs drug...

journal_title：Journal of medicinal chemistry

authors： Litty FA,Gudd J,Girreser U,Clement B,Schade D

更新日期：2016-09-08 00:00:00

abstract：:The variation in amino acid sequence within sets of peptides is described by three principal properties, z1, z2, and z3, per varied amino acid position. These principal properties are derived from a principal components analysis of a matrix of 29 physicochemical variables for the 20 coded (in mRNA) amino acids. The sc...

journal_title：Journal of medicinal chemistry

authors： Hellberg S,Sjöström M,Skagerberg B,Wold S

更新日期：1987-07-01 00:00:00

abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...

journal_title：Journal of medicinal chemistry

authors： Bach NJ,Kornfeld EC,Dorman DE

更新日期：1977-08-01 00:00:00

abstract：:Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-...

journal_title：Journal of medicinal chemistry

authors： Hoekstra WJ,Maryanoff BE,Damiano BP,Andrade-Gordon P,Cohen JH,Costanzo MJ,Haertlein BJ,Hecker LR,Hulshizer BL,Kauffman JA,Keane P,McComsey DF,Mitchell JA,Scott L,Shah RD,Yabut SC

更新日期：1999-12-16 00:00:00

abstract：:We have derivatized Momordica saponins (MS) I and II through their coupling at C3 glucuronic acid site with dodecylamine. The derivatives show significantly different immunostimulant activity profiles from their respective natural parent saponins. In particular, adjuvant VSA-1 (5), the derivative of MS I, potentiates ...

journal_title：Journal of medicinal chemistry

authors： Wang P,Ding X,Kim H,Škalamera Đ,Michalek SM,Zhang P

更新日期：2019-11-14 00:00:00

abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...

journal_title：Journal of medicinal chemistry

authors： Na Y,Li VS,Nakanishi Y,Bastow KF,Kohn H

更新日期：2001-10-11 00:00:00

abstract：:During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended thiomorpho...

journal_title：Journal of medicinal chemistry

authors： Barbachyn MR,Hutchinson DK,Brickner SJ,Cynamon MH,Kilburn JO,Klemens SP,Glickman SE,Grega KC,Hendges SK,Toops DS,Ford CW,Zurenko GE

更新日期：1996-02-02 00:00:00

abstract：:A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDA...

journal_title：Journal of medicinal chemistry

authors： Marson CM,Matthews CJ,Atkinson SJ,Lamadema N,Thomas NS

更新日期：2015-09-10 00:00:00