Synthesis of 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil and its amino analogue, new potent uridine phosphorylase inhibitors with high water solubility.

abstract：:Protein arginine methyltransferase 1 (PRMT1) is involved in many biological activities, such as gene transcription, signal transduction, and RNA processing. Overexpression of PRMT1 is related to cardiovascular diseases, kidney diseases, and cancers; therefore, selective PRMT1 inhibitors serve as chemical probes to inv...

journal_title：Journal of medicinal chemistry

authors： Hu H,Owens EA,Su H,Yan L,Levitz A,Zhao X,Henary M,Zheng YG

更新日期：2015-02-12 00:00:00

abstract：:In developing probes for detecting beta-amyloid (Abeta) plaques in the brain of Alzheimer's disease (AD), we have synthesized 1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (5, BSB). Due to the presence of two double bonds, formation of four different isomers is possible. Four isomers, E,E-5, E,Z-5, Z,E-5,...

journal_title：Journal of medicinal chemistry

authors： Lee CW,Zhuang ZP,Kung MP,Plössl K,Skovronsky D,Gur T,Hou C,Trojanowski JQ,Lee VM,Kung HF

更新日期：2001-07-05 00:00:00

abstract：:Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely com...

journal_title：Journal of medicinal chemistry

authors： Murage EN,Gao G,Bisello A,Ahn JM

更新日期：2010-09-09 00:00:00

abstract：:The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis a...

journal_title：Journal of medicinal chemistry

authors： Matyskiela ME,Zhang W,Man HW,Muller G,Khambatta G,Baculi F,Hickman M,LeBrun L,Pagarigan B,Carmel G,Lu CC,Lu G,Riley M,Satoh Y,Schafer P,Daniel TO,Carmichael J,Cathers BE,Chamberlain PP

更新日期：2018-01-25 00:00:00

abstract：:We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more p...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Zou H,Lin S,Lin H,Soh RT,Lim FH,Koh WL,Li J,Lakshminarayanan R,Verma C,Tan DT,Cao D,Beuerman RW,Liu S

更新日期：2016-01-14 00:00:00

abstract：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...

journal_title：Journal of medicinal chemistry

authors： Krogsgaard-Larsen P,Nielsen EO,Curtis DR

更新日期：1984-05-01 00:00:00

abstract：:The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...

journal_title：Journal of medicinal chemistry

authors： Eich E,Pertz H,Kaloga M,Schulz J,Fesen MR,Mazumder A,Pommier Y

更新日期：1996-01-05 00:00:00

abstract：:Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...

journal_title：Journal of medicinal chemistry

authors： Efange SM,Khare A,Parsons SM,Bau R,Metzenthin T

更新日期：1993-04-16 00:00:00

abstract：:A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC80, the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity ...

journal_title：Journal of medicinal chemistry

authors： Diana GD,Volkots DL,Nitz TJ,Bailey TR,Long MA,Vescio N,Aldous S,Pevear DC,Dutko FJ

更新日期：1994-07-22 00:00:00

abstract：:The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antim...

journal_title：Journal of medicinal chemistry

authors： Pettit GR,Singh SB,Boyd MR,Hamel E,Pettit RK,Schmidt JM,Hogan F

更新日期：1995-05-12 00:00:00

abstract：:In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it em...

journal_title：Journal of medicinal chemistry

authors： Catarzi D,Colotta V,Varano F,Calabri FR,Filacchioni G,Galli A,Costagli C,Carlà V

更新日期：2004-01-01 00:00:00

abstract：:In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid,...

journal_title：Journal of medicinal chemistry

authors： Li Y,Zhu YM,Jiang HJ,Pan JP,Wu GS,Wu JM,Shi YL,Yang JD,Wu BA

更新日期：2000-04-20 00:00:00

abstract：:A number of 7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3d-d]pyrimidine derivatives that are structurally related to toyocamycin and sangivamycin and the seco nucleosides of tubercidin, toyocamycin, and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-brom...

journal_title：Journal of medicinal chemistry

authors： Gupta PK,Daunert S,Nassiri MR,Wotring LL,Drach JC,Townsend LB

更新日期：1989-02-01 00:00:00

abstract：:Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of E...

journal_title：Journal of medicinal chemistry

authors： Heightman TD,Berdini V,Braithwaite H,Buck IM,Cassidy M,Castro J,Courtin A,Day JEH,East C,Fazal L,Graham B,Griffiths-Jones CM,Lyons JF,Martins V,Muench S,Munck JM,Norton D,O'Reilly M,Palmer N,Pathuri P,Reader M,R

更新日期：2018-06-14 00:00:00

abstract：:The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn ...

journal_title：Journal of medicinal chemistry

authors： Kudrevich S,Brasseur N,La Madeleine C,Gilbert S,van Lier JE

更新日期：1997-11-21 00:00:00

abstract：:The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and the subsequent incorporation of fragment 47 to the scaffold...

journal_title：Journal of medicinal chemistry

authors： Li Z,Xiao S,Yang Y,Chen C,Lu T,Chen Z,Jiang H,Chen S,Luo C,Zhou B

更新日期：2020-04-23 00:00:00

abstract：:A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7[(1R,4R)-2,5-...

journal_title：Journal of medicinal chemistry

authors： Remuzon P,Bouzard D,Guiol C,Jacquet JP

更新日期：1992-07-24 00:00:00

abstract：:The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...

journal_title：Journal of medicinal chemistry

authors： Carvalho JF,Silva MM,Moreira JN,Simões S,Sá e Melo ML

更新日期：2010-11-11 00:00:00

abstract：:ERAP1 is an endoplasmic reticulum-resident zinc aminopeptidase that plays an important role in the immune system by trimming peptides for loading onto major histocompatibility complex proteins. Here, we report discovery of the first inhibitors selective for ERAP1 over its paralogues ERAP2 and IRAP. Compound 1 (N-(N-(2...

journal_title：Journal of medicinal chemistry

authors： Maben Z,Arya R,Rane D,An WF,Metkar S,Hickey M,Bender S,Ali A,Nguyen TT,Evnouchidou I,Schilling R,Stratikos E,Golden J,Stern LJ

更新日期：2020-01-09 00:00:00

abstract：:A common dichotomy exists in inhibitor design: should the compounds be designed to block the enzymes of animals in the preclinical studies or to inhibit the human enzyme? We report that a single mutation of Leu-337 in rat neuronal nitric oxide synthase (nNOS) to His makes the enzyme resemble human nNOS more than rat n...

journal_title：Journal of medicinal chemistry

authors： Fang J,Ji H,Lawton GR,Xue F,Roman LJ,Silverman RB

更新日期：2009-07-23 00:00:00

abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...

journal_title：Journal of medicinal chemistry

authors： van Wijngaarden I,Kruse CG,van Hes R,van der Heyden JA,Tulp MT

更新日期：1987-11-01 00:00:00

abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...

journal_title：Journal of medicinal chemistry

authors： Rickenbacher U,McKinney JD,Oatley SJ,Blake CC

更新日期：1986-05-01 00:00:00

abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...

journal_title：Journal of medicinal chemistry

authors： Conti P,De Amici M,De Sarro G,Rizzo M,Stensbøl TB,Bräuner-Osborne H,Madsen U,Toma L,De Micheli C

更新日期：1999-10-07 00:00:00

abstract：:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...

journal_title：Journal of medicinal chemistry

authors： Bijelic A,Theiner S,Keppler BK,Rompel A

更新日期：2016-06-23 00:00:00

abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Shibata Y,Wataya Y,Tsuchiya K,Masuyama A,Nojima M

更新日期：1999-07-15 00:00:00

abstract：:Spiropyrimidinetriones are a novel class of antibacterial agents that target the bacterial type II topoisomerase via a new mode of action. Compound ETX0914 is thus far the only drug from this class that is being evaluated in clinical trials. To improve the antibacterial activity and pharmacokinetic properties of ETX09...

journal_title：Journal of medicinal chemistry

authors： Shi C,Zhang Y,Wang T,Lu W,Zhang S,Guo B,Chen Q,Luo C,Zhou X,Yang Y

更新日期：2019-03-28 00:00:00

abstract：:Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel ant...

journal_title：Journal of medicinal chemistry

authors： Dhananjeyan MR,Milev YP,Kron MA,Nair MG

更新日期：2005-04-21 00:00:00

abstract：:A series of twenty alkyl-, halo-, and methoxy-aryl-substituted 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids were synthesized. The new compounds, called CSAB, suppressed proliferation of human cervix carcinoma, HeLa cells, in vitro in a concentration range of 0.644 to 29.48 microM/L. Two compounds exhibit ant...

journal_title：Journal of medicinal chemistry

authors： Drakulić BJ,Juranić ZD,Stanojković TP,Juranić IO

更新日期：2005-08-25 00:00:00

abstract：:FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophospho...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Uecker A,Sellmer A,Cénac C,Höcher H,Pongratz H,Eichhorn E,Hufsky H,Trümpler A,Sicker M,Heidel F,Fischer T,Stocking C,Elz S,Böhmer FD,Dove S

更新日期：2006-06-01 00:00:00

abstract：:Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the centr...

journal_title：Journal of medicinal chemistry

authors： Richardson RD,Ma G,Oyola Y,Zancanella M,Knowles LM,Cieplak P,Romo D,Smith JW

更新日期：2008-09-11 00:00:00