Fumarranol, a rearranged fumagillin analogue that inhibits angiogenesis in vivo.

abstract：:For disease network intervention, up-regulating enzyme activities is equally as important as down-regulating activities. However, the design of enzyme activators presents a challenging route for drug discovery. Previous studies have suggested that activating 15-lipoxygenase (15-LOX) is a promising strategy to interven...

journal_title：Journal of medicinal chemistry

authors： Meng H,McClendon CL,Dai Z,Li K,Zhang X,He S,Shang E,Liu Y,Lai L

更新日期：2016-05-12 00:00:00

abstract：:An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (R...

journal_title：Journal of medicinal chemistry

authors： Kuo CL,Assefa H,Kamath S,Brzozowski Z,Slawinski J,Saczewski F,Buolamwini JK,Neamati N

更新日期：2004-01-15 00:00:00

abstract：:The regulation of lipid metabolism and it's effect on glucose control and diabetes has received intense interest. Hormone-sensitive lipase (HSL) is a vital enzyme in lipid metabolism. A series of novel pyrrolopyrazinediones has been discovered that demonstrate submicromolar activity both in the enzyme assay and in a (...

journal_title：Journal of medicinal chemistry

authors： Slee DH,Bhat AS,Nguyen TN,Kish M,Lundeen K,Newman MJ,McConnell SJ

更新日期：2003-03-27 00:00:00

abstract：:We have synthesized several 7alpha-fluoro (F) and 7alpha-iodo (I) analogues of 5alpha-dihydrotestosterone (5alpha-DHT) and 19-nor-5alpha-dihydrotestosterone (5alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in an in vitro assay with cells that have been engineered to ...

journal_title：Journal of medicinal chemistry

authors： Labaree DC,Hoyte RM,Nazareth LV,Weigel NL,Hochberg RB

更新日期：1999-06-03 00:00:00

abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxy...

journal_title：Journal of medicinal chemistry

authors： Yang D,Zhang S,Fang X,Guo L,Hu N,Guo Z,Li X,Yang S,He JC,Kuang C,Yang Q

更新日期：2019-10-24 00:00:00

abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

journal_title：Journal of medicinal chemistry

authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

更新日期：2004-01-29 00:00:00

abstract：:We report X-ray crystallographic structures of three inhibitors bound to dehydrosqualene synthase from Staphylococcus aureus: 1 (BPH-651), 2 (WC-9), and 3 (SQ-109). Compound 2 binds to the S2 site with its -SCN group surrounded by four hydrogen bond donors. With 1, we report two structures: in both, the quinuclidine h...

journal_title：Journal of medicinal chemistry

authors： Lin FY,Liu YL,Li K,Cao R,Zhu W,Axelson J,Pang R,Oldfield E

更新日期：2012-05-10 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：:A number of new 4(1H)-quinazolinones were synthesized and evaluated in the carrageenin-induced paw edema test. Most of the compounds were obtained by the cyclization of the appropriately substituted anthranilamides with acid chlorides, followed by further chemical transformation. Structure-activity data suggest that 2...

journal_title：Journal of medicinal chemistry

authors： Ozaki K,Yamada Y,Oine T,Ishizuka T,Iwasawa Y

更新日期：1985-05-01 00:00:00

abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...

journal_title：Journal of medicinal chemistry

authors： Kelley JL,Koble CS,Davis RG,McLean EW,Soroko FE,Cooper BR

更新日期：1995-09-29 00:00:00

abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...

journal_title：Journal of medicinal chemistry

authors： Chern JW,Tao PL,Wang KC,Gutcait A,Liu SW,Yen MH,Chien SL,Rong JK

更新日期：1998-08-13 00:00:00

abstract：:Sixteen long-chain arylpiperazines bearing the fluorescent moiety 2-phenylimidazo[1,2-a]pyridine were synthesized as fluorescent dopamine D3 receptors ligands (385 nM < Ki < 0.72 nM). The most potent D3 compounds 15a and 19a (Ki = 1.6 and 0.72 nM, respectively) showed good Stokes shift and high quantum yield in ethano...

journal_title：Journal of medicinal chemistry

authors： Leopoldo M,Lacivita E,Passafiume E,Contino M,Colabufo NA,Berardi F,Perrone R

更新日期：2007-10-04 00:00:00

abstract：:Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the comp...

journal_title：Journal of medicinal chemistry

authors： Li R,Farmer PS,Xie M,Quilliam MA,Pleasance S,Howlett SE,Yeung PK

更新日期：1992-08-21 00:00:00

abstract：:A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...

journal_title：Journal of medicinal chemistry

authors： D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

更新日期：2018-04-12 00:00:00

abstract：:The synthesis is described of a series of analogues of the potent thymidylate synthase (TS) inhibitor, N-[4-[N-[(3,4-dihydro-2, 7-dimethyl-4-oxo-6-quinazolinyl)methyl]-N-prop-2-ynylamino]-2-f luorob enzoyl]-L-glutamic acid (4, ZM214888), in which the glutamic acid moiety is replaced by homologous amino acids and alpha...

journal_title：Journal of medicinal chemistry

authors： Marsham PR,Wardleworth JM,Boyle FT,Hennequin LF,Kimbell R,Brown M,Jackman AL

更新日期：1999-09-23 00:00:00

abstract：:6-Chloropurine derivatives of gamma-(Z)-ethylidene-2,3-dimethoxybutenolide 3a, gamma-(Z)-ethylidene-2-methoxy-3-(4-nitro)benzyloxybutenolide 3b, gamma-(Z)-ethylidene-2-(4-nitro)benzyloxy-3-methoxybutenolide 3c, gamma-(Z)-ethylidene-2,3-di(4-nitro)benzyloxybutenolide 3d, and dimethylphosphono-gamma-(Z)-ethylidene-2,3-d...

journal_title：Journal of medicinal chemistry

authors： Hakimelahi GH,Mei NW,Moosavi-Movahedi AA,Davari H,Hakimelahi S,King KY,Hwu JR,Wen YS

更新日期：2001-05-24 00:00:00

abstract：:The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less...

journal_title：Journal of medicinal chemistry

authors： Reinke RA,King PJ,Victoria JG,McDougall BR,Ma G,Mao Y,Reinecke MG,Robinson WE Jr

更新日期：2002-08-15 00:00:00

abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...

journal_title：Journal of medicinal chemistry

authors： Clark RD,Berger J,Garg P,Weinhardt KK,Spedding M,Kilpatrick AT,Brown CM,MacKinnon AC

更新日期：1990-02-01 00:00:00

abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...

journal_title：Journal of medicinal chemistry

authors： Smith PA,Sorich MJ,McKinnon RA,Miners JO

更新日期：2003-04-24 00:00:00

abstract：:Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine o...

journal_title：Journal of medicinal chemistry

authors： Nishimura K,Lu X,Silverman RB

更新日期：1993-02-19 00:00:00

abstract：:Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most p...

journal_title：Journal of medicinal chemistry

authors： Liu F,Barsyte-Lovejoy D,Allali-Hassani A,He Y,Herold JM,Chen X,Yates CM,Frye SV,Brown PJ,Huang J,Vedadi M,Arrowsmith CH,Jin J

更新日期：2011-09-08 00:00:00

abstract：:The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that ...

journal_title：Journal of medicinal chemistry

authors： LaPlante SR,Carson R,Gillard J,Aubry N,Coulombe R,Bordeleau S,Bonneau P,Little M,O'Meara J,Beaulieu PL

更新日期：2013-06-27 00:00:00

abstract：:With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...

journal_title：Journal of medicinal chemistry

authors： Sun X,Rodriguez M,Zeckner D,Sachs B,Current W,Boyer R,Paschal J,McMillian C,Chen SH

更新日期：2001-08-02 00:00:00

abstract：:Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-be...

journal_title：Journal of medicinal chemistry

authors： Peglion JL,Canton H,Bervoets K,Audinot V,Brocco M,Gobert A,Le Marouille-Girardon S,Millan MJ

更新日期：1995-09-29 00:00:00

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response. ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Ballard P,Bardelle C,Cockerill M,Colclough N,Critchlow SE,Debreczeni J,Fairley G,Fillery S,Graham MA,Goodwin L,Guichard S,Hudson K,Ward RA,Whittaker D

更新日期：2015-03-26 00:00:00

abstract：:The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as w...

journal_title：Journal of medicinal chemistry

authors： Giraud F,Alves G,Debiton E,Nauton L,Théry V,Durieu E,Ferandin Y,Lozach O,Meijer L,Anizon F,Pereira E,Moreau P

更新日期：2011-07-14 00:00:00

abstract：:We present a novel method to better investigate adverse drug reactions in chemical space. By integrating data sources about adverse drug reactions of drugs with an established cheminformatics modeling method, we generate a data set that is then visualized with a systems biology tool. Thereby new insights into undesire...

journal_title：Journal of medicinal chemistry

authors： Scheiber J,Jenkins JL,Sukuru SC,Bender A,Mikhailov D,Milik M,Azzaoui K,Whitebread S,Hamon J,Urban L,Glick M,Davies JW

更新日期：2009-05-14 00:00:00

abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...

journal_title：Journal of medicinal chemistry

authors： Das U,Pati HN,Sakagami H,Hashimoto K,Kawase M,Balzarini J,De Clercq E,Dimmock JR

更新日期：2011-05-12 00:00:00

abstract：:A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library wa...

journal_title：Journal of medicinal chemistry

authors： Goto Y,Arai-Otsuki S,Tachibana Y,Ichikawa D,Ozaki S,Takahashi H,Iwasawa Y,Okamoto O,Okuda S,Ohta H,Sagara T

更新日期：2006-02-09 00:00:00