Prostaglandins and congeners. 16. Synthesis and bronchodilator activity of dl-11-doexy-3-thiaprostaglandins.

abstract：:Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...

journal_title：Journal of medicinal chemistry

authors： Tamura R,Balabanova A,Frakes SA,Bargmann A,Grimm J,Koch TH,Yin H

更新日期：2019-02-28 00:00:00

abstract：:Major urinary metabolites of carbidopa have been identified. Estimates were made based on the recovery or radio activity or by glc analysis of pooled urine of the amounts of the urinary metabolites II (2-methyl-3'-methoxy-4'-hydroxyphenylpropionic acid), III (2-methyl-3,4-dihydroxyphenylpropionic acid), IV (3,4-dihydr...

journal_title：Journal of medicinal chemistry

authors： Vickers S,Stuart EK,Hucker HB

更新日期：1975-02-01 00:00:00

abstract：:Fluorescence spectrometry data by Tyulmenkov and Klinge (Arch. Biochem. Biophys. 2000, 381, 135-142) suggest the presence of a second binding site in both subtypes ER alpha and ER beta of the estrogen receptor (ER). A cavity previously described as a solvent channel was located in close proximity to the steroid bindin...

journal_title：Journal of medicinal chemistry

authors： van Hoorn WP

更新日期：2002-01-31 00:00:00

abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Mitscher LA,Mullican MD,Drake SD,Kitos P

更新日期：1985-10-01 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...

journal_title：Journal of medicinal chemistry

authors： Bertoletti N,Braun F,Lepage M,Möller G,Adamski J,Heine A,Klebe G,Marchais-Oberwinkler S

更新日期：2016-07-28 00:00:00

abstract：:The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]q...

journal_title：Journal of medicinal chemistry

authors： Wadsworth HJ,Jenkins SM,Orlek BS,Cassidy F,Clark MS,Brown F,Riley GJ,Graves D,Hawkins J,Naylor CB

更新日期：1992-04-03 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：:We present the first report of the application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to hydroxy-containing drug derivatives. In particular, we applied this strategy to the highly lipophilic antiviral drug family of bicyclic furanopyrimidine nucleoside analogues (BCNA) in order to improve t...

journal_title：Journal of medicinal chemistry

authors： Diez-Torrubia A,Balzarini J,Andrei G,Snoeck R,De Meester I,Camarasa MJ,Velázquez S

更新日期：2011-03-24 00:00:00

abstract：:The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...

journal_title：Journal of medicinal chemistry

authors： Jadhav A,Ferreira RS,Klumpp C,Mott BT,Austin CP,Inglese J,Thomas CJ,Maloney DJ,Shoichet BK,Simeonov A

更新日期：2010-01-14 00:00:00

abstract：:Over 25 selected naphthalenesulfonic acid derivatives were evaluated for their inhibitory effect on two different functional domains of the HIV-1 reverse transcriptase (RT), namely the ribonuclease H and DNA polymerase activities. Most of the analogues were found to be either specific toward the DNA polymerase activit...

journal_title：Journal of medicinal chemistry

authors： Mohan P,Loya S,Avidan O,Verma S,Dhindsa GS,Wong MF,Huang PP,Yashiro M,Baba M,Hizi A

更新日期：1994-08-05 00:00:00

abstract：:The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...

journal_title：Journal of medicinal chemistry

authors： Thurmond RL,Beavers MP,Cai H,Meduna SP,Gustin DJ,Sun S,Almond HJ,Karlsson L,Edwards JP

更新日期：2004-09-23 00:00:00

abstract：:A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K(i) values ranged from 0.05 nM to >100 nM. (R)-N-(2-Fluoroethyl)-3-pi...

journal_title：Journal of medicinal chemistry

authors： Skaddan MB,Kilbourn MR,Snyder SE,Sherman PS,Desmond TJ,Frey KA

更新日期：2000-11-16 00:00:00

abstract：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...

journal_title：Journal of medicinal chemistry

authors： Borsari C,Rageot D,Dall'Asen A,Bohnacker T,Melone A,Sele AM,Jackson E,Langlois JB,Beaufils F,Hebeisen P,Fabbro D,Hillmann P,Wymann MP

更新日期：2019-09-26 00:00:00

abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Teller S,Pongratz H,Hufsky H,Sellmer A,Botzki A,Uecker A,Beckers T,Baasner S,Schächtele C,Uberall F,Kassack MU,Dove S,Böhmer FD

更新日期：2002-02-28 00:00:00

abstract：:A series of cis and trans bicyclic lactones was prepared as congeners of podophyllotoxin (1) and evaluated as antimitotic agents both in cell cultures grown in vitro and in an in vitro protein binding assay. All compounds displayed insignificant activity-a result which may reflect insufficient structural similarity to...

journal_title：Journal of medicinal chemistry

authors： Smissman EE,Murray RJ,McChesney JD,Houston LL,Pazdernik TL

更新日期：1976-01-01 00:00:00

abstract：:Optimization of the pharmacokinetic properties for a series of benzoxazolone derivatives led to the identification of 9b, which showed anxiolytic effect in a rat model. However, 9b, like known benzodiazepines, induced motor impairment. Investigation into the cause of this unexpected side effect and management of 9b of...

journal_title：Journal of medicinal chemistry

authors： Fukaya T,Ishiyama T,Baba S,Masumoto S

更新日期：2013-10-24 00:00:00

abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Fry DW,Kraker AJ,Denny WA

更新日期：1994-03-04 00:00:00

abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...

journal_title：Journal of medicinal chemistry

authors： Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JC

更新日期：1994-12-09 00:00:00

abstract：:By use of standard cuprate methodology, a series of 18-cycloalkyl analogues of enisoprost was prepared in an effort to impede omega chain metabolism and prolong duration of gastric antisecretory activity. An initial product of omega chain oxidation, the C-20 hydroxy analogue, was also synthesized for pharmacological c...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Gasiecki AF,Perkins WE,Gullikson GW,Jones PH,Bauer RF

更新日期：1989-05-01 00:00:00

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 00:00:00

abstract：:1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentration. Replacement of one phenyl ring of 1-[2-(diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings, such as 2-thien...

journal_title：Journal of medicinal chemistry

authors： De Martino G,La Regina G,Di Pasquali A,Ragno R,Bergamini A,Ciaprini C,Sinistro A,Maga G,Crespan E,Artico M,Silvestri R

更新日期：2005-06-30 00:00:00

abstract：:A variety of nitroheterocyclic carbamate prodrugs of phenylenediamine mustard and 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3H-benz[e]indoline (amino-seco-CBI-TMI), covering a wide range of reduction potential, were prepared and evaluated for use in gene-directed enzyme prodrug ther...

journal_title：Journal of medicinal chemistry

authors： Hay MP,Anderson RF,Ferry DM,Wilson WR,Denny WA

更新日期：2003-12-04 00:00:00

abstract：:On the basis of our previous observation that N1-alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. N1-Allyl...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Goon DJ,Shirota FN

更新日期：1994-11-25 00:00:00

abstract：:The TOP2 poison etoposide has been implicated in the generation of secondary malignancies during cancer treatment. Structural similarities between TOP2 isoforms challenge the rational design of isoform-specific poisons to further delineate these processes. Herein, we describe the synthesis and biological evaluation of...

journal_title：Journal of medicinal chemistry

authors： Mariani A,Bartoli A,Atwal M,Lee KC,Austin CA,Rodriguez R

更新日期：2015-06-11 00:00:00

abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

journal_title：Journal of medicinal chemistry

authors： Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

更新日期：2013-10-24 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：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...

journal_title：Journal of medicinal chemistry

authors： Xu Y,Jiang G,Tsukahara R,Fujiwara Y,Tigyi G,Prestwich GD

更新日期：2006-08-24 00:00:00

abstract：:As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N(6)-, 2-amino-N(6)-, and N(2)-substituted adenosine analogues were synthesized and tested to establish structure-activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate ki...

journal_title：Journal of medicinal chemistry

authors： Bressi JC,Choe J,Hough MT,Buckner FS,Van Voorhis WC,Verlinde CL,Hol WG,Gelb MH

更新日期：2000-11-02 00:00:00

abstract：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Omnaas JR,Lomize A,Heyl DL,Nordan I,Mousigian C,Davis P,Porreca F

更新日期：1994-12-09 00:00:00