A novel class of "GABAergic" agents: 1-aryl-3-(aminoalkylidene)oxindoles.

abstract：:alpha-Ethynyl- and alpha-vinylornithine were designed and synthesized as potential enzyme-activated inhibitors of mammalian ornithine decarboxylase. These two new inhibitors produce both immediate and time-dependent inhibition of rat liver ornithine decarboxylase in vitro. The inhibitions exhibition saturation kinetic...

journal_title：Journal of medicinal chemistry

authors： Danzin C,Casara P,Claverie N,Metcalf BW

更新日期：1981-01-01 00:00:00

abstract：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Vodonick SM,Criscione KR,McLeish MJ,Grunewald GL

更新日期：2004-08-26 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：:Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compound...

journal_title：Journal of medicinal chemistry

authors： Gurney ME,Nugent RA,Mo X,Sindac JA,Hagen TJ,Fox D 3rd,O'Donnell JM,Zhang C,Xu Y,Zhang HT,Groppi VE,Bailie M,White RE,Romero DL,Vellekoop AS,Walker JR,Surman MD,Zhu L,Campbell RF

更新日期：2019-05-23 00:00:00

abstract：:4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 microM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prost...

journal_title：Journal of medicinal chemistry

authors： Meanwell NA,Rosenfeld MJ,Trehan AK,Wright JJ,Brassard CL,Buchanan JO,Federici ME,Fleming JS,Gamberdella M,Zavoico GB

更新日期：1992-09-18 00:00:00

abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...

journal_title：Journal of medicinal chemistry

authors： Havlícek L,Hanus J,Veselý J,Leclerc S,Meijer L,Shaw G,Strnad M

更新日期：1997-02-14 00:00:00

abstract：:A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha4beta1/VCAM-1 and alpha4beta7/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the p...

journal_title：Journal of medicinal chemistry

authors： Gong Y,Barbay JK,Dyatkin AB,Miskowski TA,Kimball ES,Prouty SM,Fisher MC,Santulli RJ,Schneider CR,Wallace NH,Ballentine SA,Hageman WE,Masucci JA,Maryanoff BE,Damiano BP,Andrade-Gordon P,Hlasta DJ,Hornby PJ,He W

更新日期：2006-06-01 00:00:00

abstract：:Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of proca...

journal_title：Journal of medicinal chemistry

authors： Zemlicka J,Fernandez-Moyano MC,Ariatti M,Zurenko GE,Grady JE,Ballesta JP

更新日期：1993-04-30 00:00:00

abstract：:3',5'-Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger that regulates numerous biological processes under physiological and pathological conditions, including cancer, diabetes, heart failure, inflammation, and neurological disorders. In the past, all effects of cAMP were initially believed to be med...

journal_title：Journal of medicinal chemistry

authors： Chen H,Wild C,Zhou X,Ye N,Cheng X,Zhou J

更新日期：2014-05-08 00:00:00

abstract：:We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localiz...

journal_title：Journal of medicinal chemistry

authors： de Jonge MR,Koymans LM,Vinkers HM,Daeyaert FF,Heeres J,Lewi PJ,Janssen PA

更新日期：2005-03-24 00:00:00

abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Cheng JC,Ishiguro K,Sartorelli AC

更新日期：1985-09-01 00:00:00

abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...

journal_title：Journal of medicinal chemistry

authors： Chawla RR,Freed JJ,Kappler F,Hampton A

更新日期：1986-05-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and c...

journal_title：Journal of medicinal chemistry

authors： Ohashi M,Oyama T,Nakagome I,Satoh M,Nishio Y,Nobusada H,Hirono S,Morikawa K,Hashimoto Y,Miyachi H

更新日期：2011-01-13 00:00:00

abstract：:Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids, oligosaccharides, proteins, and glycoproteins. Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes. While often catalytically competent, the mutated enzym...

journal_title：Journal of medicinal chemistry

authors： Boyd RE,Lee G,Rybczynski P,Benjamin ER,Khanna R,Wustman BA,Valenzano KJ

更新日期：2013-04-11 00:00:00

abstract：:Several novel azulene-containing retinoids were prepared and evaluated for their ability to suppress carcinogen-induced neoplastic transformation and to concomitantly up-regulate gap junctional communication in the in vitro mouse fibroblast C3H/10T1/2 cell bioassay. The azulenic retinoids were divided into two groups:...

journal_title：Journal of medicinal chemistry

authors： Asato AE,Peng A,Hossain MZ,Mirzadegan T,Bertram JS

更新日期：1993-10-15 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：:The lack of molecules endowed with selective and potent agonistic activity toward the hA2B adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential. We report the design and the synthesis of the first potent (EC50 in the nanomolar range) an...

journal_title：Journal of medicinal chemistry

authors： Baraldi PG,Preti D,Tabrizi MA,Fruttarolo F,Romagnoli R,Carrion MD,Cara LC,Moorman AR,Varani K,Borea PA

更新日期：2007-01-25 00:00:00

abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...

journal_title：Journal of medicinal chemistry

authors： Hall A,Provins L,Valade A

更新日期：2019-01-10 00:00:00

abstract：:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active aga...

journal_title：Journal of medicinal chemistry

authors： Bolognese A,Correale G,Manfra M,Lavecchia A,Novellino E,Pepe S

更新日期：2006-08-24 00:00:00

abstract：:Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl...

journal_title：Journal of medicinal chemistry

authors： Policarpo RL,Decultot L,May E,Kuzmič P,Carlson S,Huang D,Chu V,Wright BA,Dhakshinamoorthy S,Kannt A,Rani S,Dittakavi S,Panarese JD,Gaudet R,Shair MD

更新日期：2019-11-14 00:00:00

abstract：:(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D- arabinofuranosyl)-5-iodouracil to give 1- (2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)eth yny l] uracil. Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. T...

journal_title：Journal of medicinal chemistry

authors： Robins MJ,Manfredini S,Wood SG,Wanklin RJ,Rennie BA,Sacks SL

更新日期：1991-07-01 00:00:00

abstract：:Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days...

journal_title：Journal of medicinal chemistry

authors： Singh C,Malik H,Puri SK

更新日期：2006-05-04 00:00:00

abstract：:The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was obse...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung HF,Billings J,Guo YZ,Wu Y,Shih J

更新日期：1989-03-01 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：: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：:2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives int...

journal_title：Journal of medicinal chemistry

authors： Frecentese F,Sosic A,Saccone I,Gamba E,Link K,Miola A,Cappellini M,Cattelan MG,Severino B,Fiorino F,Magli E,Corvino A,Perissutti E,Fabris D,Gatto B,Caliendo G,Santagada V

更新日期：2016-03-10 00:00:00

abstract：:A series of analogues of Pro-Leu-Gly-NH2 (PLG) in which the leucine residue has been replaced with the aliphatic amino acids L-isoleucine, L-2-aminohexanoic acid (Ahx), L-2-aminopentanoic acid, and L-2-aminobutanoic acid and the aromatic amino acids L-phenylalanine, L-phenylglycine, L- and D-2-amino-4-phenylbutanoic a...

journal_title：Journal of medicinal chemistry

authors： Johnson RL,Bontems RJ,Yang KE,Mishra RK

更新日期：1990-06-01 00:00:00

abstract：:Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been developed using comparative molecular field analysis (CoMFA) on a large data set (118 compounds) of diverse cyclic urea derivatives as protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray crystal str...

journal_title：Journal of medicinal chemistry

authors： Debnath AK

更新日期：1999-01-28 00:00:00

abstract：:The therapeutic success of peptidic GLP-1 receptor agonists for treatment of type 2 diabetes mellitus (T2DM) motivated our search for orally bioavailable small molecules that can activate the GLP-1 receptor (GLP-1R) as a well-validated target for T2DM. Here, the discovery and characterization of a potent and selective...

journal_title：Journal of medicinal chemistry

authors： Méndez M,Matter H,Defossa E,Kurz M,Lebreton S,Li Z,Lohmann M,Löhn M,Mors H,Podeschwa M,Rackelmann N,Riedel J,Safar P,Thorpe DS,Schäfer M,Weitz D,Breitschopf K

更新日期：2020-03-12 00:00:00

abstract：:By modification of key carboxylate, hydrophobic, and zinc-binding groups projected from a sterically restricted terphenyl scaffold, a series of simple and nonpeptide mimetics of the Cys-Val-Ile-Met tetrapeptide substrate of protein farnesyltransferase (FTase) have been designed and synthesized. A crystal structure of ...

journal_title：Journal of medicinal chemistry

authors： Ohkanda J,Lockman JW,Kothare MA,Qian Y,Blaskovich MA,Sebti SM,Hamilton AD

更新日期：2002-01-03 00:00:00