Novel chemical space exploration via natural products.

abstract：:Water soluble 2'-taxol poly(ethylene glycol) (PEG) esters have been synthesized and shown to function in vitro as prodrugs. However, in vivo experiments clearly establish that in order for these prodrugs to behave in a predictable fashion, the molecular weight of PEG must be of such magnitude so as to maintain a t1/2(...

journal_title：Journal of medicinal chemistry

authors： Greenwald RB,Gilbert CW,Pendri A,Conover CD,Xia J,Martinez A

更新日期：1996-01-19 00:00:00

abstract：:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compo...

journal_title：Journal of medicinal chemistry

authors： Graham SL,Hoffman JM,Gautheron P,Michelson SR,Scholz TH,Schwam H,Shepard KL,Smith AM,Smith RL,Sondey JM

更新日期：1990-02-01 00:00:00

abstract：:8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell ...

journal_title：Journal of medicinal chemistry

authors： Jesus AR,Dias C,Matos AM,de Almeida RF,Viana AS,Marcelo F,Ribeiro RT,Macedo MP,Airoldi C,Nicotra F,Martins A,Cabrita EJ,Jiménez-Barbero J,Rauter AP

更新日期：2014-11-26 00:00:00

abstract：:N-Aminated nucleoside complexes of cis-dichloroplatinum(II) were synthesized, and their antitumor activities against L1210 cells in mice and in vitro were studied. While the native nucleosides failed to show any antitumor activity, the complexes exhibited high antitumor activity and had no nephrotoxicity in mice. Stud...

journal_title：Journal of medicinal chemistry

authors： Maeda M,Abiko N,Uchida H,Sasaki T

更新日期：1984-04-01 00:00:00

abstract：:A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% o...

journal_title：Journal of medicinal chemistry

authors： Estrada E,Uriarte E,Montero A,Teijeira M,Santana L,De Clercq E

更新日期：2000-05-18 00:00:00

abstract：:Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we h...

journal_title：Journal of medicinal chemistry

authors： Chinen LK,Galen KP,Kuan KT,Dyszlewski ME,Ozaki H,Sawai H,Pandurangi RS,Jacobs FG,Dorshow RB,Rajagopalan R

更新日期：2008-02-28 00:00:00

abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...

journal_title：Journal of medicinal chemistry

authors： Matuszak N,Muccioli GG,Labar G,Lambert DM

更新日期：2009-12-10 00:00:00

abstract：:[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low p...

journal_title：Journal of medicinal chemistry

authors： Kohl B,Sturm E,Senn-Bilfinger J,Simon WA,Krüger U,Schaefer H,Rainer G,Figala V,Klemm K

更新日期：1992-03-20 00:00:00

abstract：:The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 co...

journal_title：Journal of medicinal chemistry

authors： Kukolja S,Pfeil JL,Draheim SE,Ott JL

更新日期：1985-12-01 00:00:00

abstract：:The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagon...

journal_title：Journal of medicinal chemistry

authors： Keck TM,John WS,Czoty PW,Nader MA,Newman AH

更新日期：2015-07-23 00:00:00

abstract：:PABA/NO is a diazeniumdiolate of structure Me(2)NN(O)=NOAr (where Ar is a 5-substituted-2,4-dinitrophenyl ring whose 5-substituent is N-methyl-p-aminobenzoic acid). It has shown activity against human ovarian cancer xenografts in mice rivaling that of cisplatin, but it is poorly soluble and relatively unstable in wate...

journal_title：Journal of medicinal chemistry

authors： Saavedra JE,Srinivasan A,Buzard GS,Davies KM,Waterhouse DJ,Inami K,Wilde TC,Citro ML,Cuellar M,Deschamps JR,Parrish D,Shami PJ,Findlay VJ,Townsend DM,Tew KD,Singh S,Jia L,Ji X,Keefer LK

更新日期：2006-02-09 00:00:00

abstract：:BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited ...

journal_title：Journal of medicinal chemistry

authors： Hu J,Tian CQ,Damaneh MS,Li Y,Cao D,Lv K,Yu T,Meng T,Chen D,Wang X,Chen L,Li J,Song SS,Huan XJ,Qin L,Shen J,Wang YQ,Miao ZH,Xiong B

更新日期：2019-09-26 00:00:00

abstract：:Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20...

journal_title：Journal of medicinal chemistry

authors： Rej RK,Wang C,Lu J,Wang M,Petrunak E,Zawacki KP,McEachern D,Fernandez-Salas E,Yang CY,Wang L,Li R,Chinnaswamy K,Wen B,Sun D,Stuckey J,Zhou Y,Chen J,Tang G,Wang S

更新日期：2020-07-09 00:00:00

abstract：:Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodolog...

journal_title：Journal of medicinal chemistry

authors： Marom H,Miller K,Bechor-Bar Y,Tsarfaty G,Satchi-Fainaro R,Gozin M

更新日期：2010-09-09 00:00:00

abstract：:Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside derivatives, followed by deprotection and anomer separation, produced the alpha- and beta-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'-difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as P-...

journal_title：Journal of medicinal chemistry

authors： Ye S,Rezende MM,Deng WP,Herbert B,Daly JW,Johnson RA,Kirk KL

更新日期：2004-02-26 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 discovery of BMS-605339 (35), a tripeptidic inhibitor of the NS3/4A enzyme, is described. This compound incorporates a cyclopropylacylsulfonamide moiety that was designed to improve the potency of carboxylic acid prototypes through the introduction of favorable nonbonding interactions within the S1' site of the pr...

journal_title：Journal of medicinal chemistry

authors： Scola PM,Wang AX,Good AC,Sun LQ,Combrink KD,Campbell JA,Chen J,Tu Y,Sin N,Venables BL,Sit SY,Chen Y,Cocuzza A,Bilder DM,D'Andrea S,Zheng B,Hewawasam P,Ding M,Thuring J,Li J,Hernandez D,Yu F,Falk P,Zhai G,S

更新日期：2014-03-13 00:00:00

abstract：:Several known alpha-amino acid analogues and a new compound, N-chloroacetylphosphoramidate, a carbamyl phosphate analogue, were screened as antitumor agents. All gave 50% growth inhibition of cultures of human epidemeroid carcinoma of the nasopharynx at dosage levels of 2-8 mug/ml while showing no activity against L12...

journal_title：Journal of medicinal chemistry

authors： Glover GI,Nelson SO,Kaeder GR

更新日期：1977-03-01 00:00:00

abstract：:Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radi...

journal_title：Journal of medicinal chemistry

authors： Baqi Y,Atzler K,Köse M,Glänzel M,Müller CE

更新日期：2009-06-25 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：:Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemist...

journal_title：Journal of medicinal chemistry

authors： Pryde DC,Maw GN,Planken S,Platts MY,Sanderson V,Corless M,Stobie A,Barber CG,Russell R,Foster L,Barker L,Wayman C,Van Der Graaf P,Stacey P,Morren D,Kohl C,Beaumont K,Coggon S,Tute M

更新日期：2006-07-13 00:00:00

abstract：:We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antid...

journal_title：Journal of medicinal chemistry

authors： Manning M,Przybylski J,Grzonka Z,Nawrocka E,Lammek B,Misicka A,Cheng LL,Chan WY,Wo NC,Sawyer WH

更新日期：1992-10-16 00:00:00

abstract：:Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase i...

journal_title：Journal of medicinal chemistry

authors： Shirai F,Mizutani A,Yashiroda Y,Tsumura T,Kano Y,Muramatsu Y,Chikada T,Yuki H,Niwa H,Sato S,Washizuka K,Koda Y,Mazaki Y,Jang MK,Yoshida H,Nagamori A,Okue M,Watanabe T,Kitamura K,Shitara E,Honma T,Umehara T,Shi

更新日期：2020-04-23 00:00:00

abstract：:Acyl carrier protein synthase (AcpS) catalyzes the transfer of the 4'-phosphopantetheinyl group from the coenzyme A to a serine residue in acyl carrier protein (ACP), thereby activating ACP, an important step in cell wall biosynthesis. The structure-based design of novel anthranilic acid inhibitors of AcpS, a potentia...

journal_title：Journal of medicinal chemistry

authors： Joseph-McCarthy D,Parris K,Huang A,Failli A,Quagliato D,Dushin EG,Novikova E,Severina E,Tuckman M,Petersen PJ,Dean C,Fritz CC,Meshulam T,DeCenzo M,Dick L,McFadyen IJ,Somers WS,Lovering F,Gilbert AM

更新日期：2005-12-15 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...

journal_title：Journal of medicinal chemistry

authors： Ali A,Reddy GS,Nalam MN,Anjum SG,Cao H,Schiffer CA,Rana TM

更新日期：2010-11-11 00:00:00

abstract：:The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipep...

journal_title：Journal of medicinal chemistry

authors： Karanewsky DS,Badia MC,Cushman DW,DeForrest JM,Dejneka T,Loots MJ,Perri MG,Petrillo EW Jr,Powell JR

更新日期：1988-01-01 00:00:00

abstract：:The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure predictio...

journal_title：Journal of medicinal chemistry

authors： Patargias G,Zitzmann N,Dwek R,Fischer WB

更新日期：2006-01-26 00:00:00

abstract：:Epigenetic regulators that exhibit aberrant enzymatic activities or expression profiles are potential therapeutic targets for cancers. Specifically, enzymes responsible for methylation at histone-3 lysine-9 (like G9a) and aberrant DNA hypermethylation (DNMTs) have been implicated in a number of cancers. Recently, mole...

journal_title：Journal of medicinal chemistry

authors： Rabal O,Sánchez-Arias JA,San José-Enériz E,Agirre X,de Miguel I,Garate L,Miranda E,Sáez E,Roa S,Martínez-Climent JA,Liu Y,Wu W,Xu M,Prosper F,Oyarzabal J

更新日期：2018-08-09 00:00:00

abstract：:The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of li...

journal_title：Journal of medicinal chemistry

authors： Ding L,Etemad-Moghadam G,Cros S,Auclair C,Meunier B

更新日期：1991-03-01 00:00:00

abstract：:Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparat...

journal_title：Journal of medicinal chemistry

authors： Bühlmayer P,Criscione L,Fuhrer W,Furet P,de Gasparo M,Stutz S,Whitebread S

更新日期：1991-10-01 00:00:00