Benzodiazepine receptor binding activity of 6,9-disubstituted purines.

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：:A series of novel CCK tetrapeptide analogues of the general formula Boc-Trp-Lys(Tac)-N(R)-(CH2)nCON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK-...

journal_title：Journal of medicinal chemistry

authors： Elliott RL,Kopecka H,Tufano MD,Shue YK,Gauri AJ,Lin CW,Bianchi BR,Miller TR,Witte DG,Stashko MA

更新日期：1994-05-27 00:00:00

abstract：:We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure-activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-...

journal_title：Journal of medicinal chemistry

authors： Zhang Z,Wu G,Xie F,Song T,Chang X

更新日期：2011-02-24 00:00:00

abstract：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorub...

journal_title：Journal of medicinal chemistry

authors： Farquhar D,Cherif A,Bakina E,Nelson JA

更新日期：1998-03-12 00:00:00

abstract：:This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% r...

journal_title：Journal of medicinal chemistry

authors： Roberts MP,Nguyen V,Ashford ME,Berghofer P,Wyatt NA,Krause-Heuer AM,Pham TQ,Taylor SR,Hogan L,Jiang CD,Fraser BH,Lengkeek NA,Matesic L,Gregoire MC,Denoyer D,Hicks RJ,Katsifis A,Greguric I

更新日期：2015-08-13 00:00:00

abstract：:Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, Mycobacterium tuberculosis (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) rende...

journal_title：Journal of medicinal chemistry

authors： Zhan W,Hsu HC,Morgan T,Ouellette T,Burns-Huang K,Hara R,Wright AG,Imaeda T,Okamoto R,Sato K,Michino M,Ramjee M,Aso K,Meinke PT,Foley M,Nathan CF,Li H,Lin G

更新日期：2019-10-24 00:00:00

abstract：:The bromodomain and extra-terminal domain (BET) family of proteins bind acetylated lysine residues on histone proteins. The four BET bromodomains-BRD2, BRD3, BRD4, and BRDT-each contain two bromodomain modules. BET bromodomain inhibition is a potential therapy for various cancers and immunoinflammatory diseases, but f...

journal_title：Journal of medicinal chemistry

authors： Law RP,Atkinson SJ,Bamborough P,Chung CW,Demont EH,Gordon LJ,Lindon M,Prinjha RK,Watson AJB,Hirst DJ

更新日期：2018-05-24 00:00:00

abstract：:We have synthesized a series of N-phenyl-N'-aralkyl and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). This intracellular enzyme is thought to be responsible for the esterification of dietary cholesterol; hence inhibition of this enzyme could reduce diet-induced hyp...

journal_title：Journal of medicinal chemistry

authors： Trivedi BK,Holmes A,Stoeber TL,Blankley CJ,Roark WH,Picard JA,Shaw MK,Essenburg AD,Stanfield RL,Krause BR

更新日期：1993-10-29 00:00:00

abstract：:Due to its function in the rate limiting initial step of the renin-angiotensin system, renin is a particularly promising target for drugs designed to control hypertension, a growing risk to health worldwide. Despite vast efforts over more than two decades, no orally efficacious renin inhibitor had reached the market. ...

journal_title：Journal of medicinal chemistry

authors： Maibaum J,Stutz S,Göschke R,Rigollier P,Yamaguchi Y,Cumin F,Rahuel J,Baum HP,Cohen NC,Schnell CR,Fuhrer W,Gruetter MG,Schilling W,Wood JM

更新日期：2007-10-04 00:00:00

abstract：:Fosmidomycin inhibits IspC (Dxr, 1-deoxy-d-xylulose 5-phosphate reductoisomerase), a key enzyme in nonmevalonate isoprenoid biosynthesis that is essential in Plasmodium falciparum. The drug has been used successfully to treat malaria patients in clinical studies, thus validating IspC as an antimalarial target. However...

journal_title：Journal of medicinal chemistry

authors： Brücher K,Gräwert T,Konzuch S,Held J,Lienau C,Behrendt C,Illarionov B,Maes L,Bacher A,Wittlin S,Mordmüller B,Fischer M,Kurz T

更新日期：2015-02-26 00:00:00

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：: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：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...

journal_title：Journal of medicinal chemistry

authors： Harrison DH,Schinazi RF,Rubin BH

更新日期：1982-12-01 00:00:00

abstract：:Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P...

journal_title：Journal of medicinal chemistry

authors： Hui KY,Holtzman EJ,Quinones MA,Hollenberg NK,Haber E

更新日期：1988-09-01 00:00:00

abstract：:Aurora kinase inhibitors have attracted a great deal of interest as a new class of antimitotic agents. We report a novel class of Aurora inhibitors based on a pentacyclic scaffold. A prototype pentacyclic inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties of each parent and...

journal_title：Journal of medicinal chemistry

authors： Rawson TE,Rüth M,Blackwood E,Burdick D,Corson L,Dotson J,Drummond J,Fields C,Georges GJ,Goller B,Halladay J,Hunsaker T,Kleinheinz T,Krell HW,Li J,Liang J,Limberg A,McNutt A,Moffat J,Phillips G,Ran Y,Safina B,U

更新日期：2008-08-14 00:00:00

abstract：:The development of very high affinity, selective, and bioavailable h5-HT(2A) receptor antagonists is described. By investigation of the optimal position for the basic nitrogen in a series of 2-phenyl-3-piperidylindoles, it was found that with the basic nitrogen at the 3-position of the piperidine it was not necessary ...

journal_title：Journal of medicinal chemistry

authors： Rowley M,Hallett DJ,Goodacre S,Moyes C,Crawforth J,Sparey TJ,Patel S,Marwood R,Patel S,Thomas S,Hitzel L,O'Connor D,Szeto N,Castro JL,Hutson PH,MacLeod AM

更新日期：2001-05-10 00:00:00

abstract：:Monophenolic (2-(dipropylamino)indans and related compounds have been synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different dopamine-rec...

journal_title：Journal of medicinal chemistry

authors： Hacksell U,Arvidsson LE,Svensson U,Nilsson JL,Wikström H,Lindberg P,Sanchez D,Hjorth S,Carlsson A,Paalzow L

更新日期：1981-04-01 00:00:00

abstract：:The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substan...

journal_title：Journal of medicinal chemistry

authors： Hirschmann R,Yao W,Cascieri MA,Strader CD,Maechler L,Cichy-Knight MA,Hynes J Jr,van Rijn RD,Sprengeler PA,Smith AB 3rd

更新日期：1996-06-21 00:00:00

abstract：:Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent γ-ca...

journal_title：Journal of medicinal chemistry

authors： Otto R,Penzis R,Gaube F,Adolph O,Föhr KJ,Warncke P,Robaa D,Appenroth D,Fleck C,Enzensperger C,Lehmann J,Winckler T

更新日期：2015-08-27 00:00:00

abstract：:We report herein the identification of the rhodium(III) complex [Rh(phq)2(MOPIP)]+ (1) as a potent and selective ATP-competitive neural precursor cell expressed, developmentally down-regulated 8 (NEDD8)-activating enzyme (NAE) inhibitor. Structure-activity relationship analysis indicated that the overall organometalli...

journal_title：Journal of medicinal chemistry

authors： Zhong HJ,Wang W,Kang TS,Yan H,Yang Y,Xu L,Wang Y,Ma DL,Leung CH

更新日期：2017-01-12 00:00:00

abstract：:A novel series of nonpeptide angiotensin II (A II) antagonists containing a pyrimidinone ring which carries a C-linked biphenyltetrazole moiety and a carboxyheteroaryl group on the 3-position have been prepared. Their affinity for the AT1 receptor was determined in a binding assay on rat adrenal cortical membranes. Th...

journal_title：Journal of medicinal chemistry

authors： Salimbeni A,Canevotti R,Paleari F,Poma D,Caliari S,Fici F,Cirillo R,Renzetti AR,Subissi A,Belvisi L

更新日期：1995-11-24 00:00:00

abstract：:Substituted 6-anilinouracils were found to be potent inhibitors of the replication-specific enzyme, DNA polymerase III, from Bacillus subtilis. Inhibition potency was maximized by inclusion of small alkyl groups or halogens in the meta and para positions of the phenyl ring; polar substituents decreased activity consi...

journal_title：Journal of medicinal chemistry

authors： Wright GE,Brown NC

更新日期：1980-01-01 00:00:00

abstract：:We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmaco...

journal_title：Journal of medicinal chemistry

authors： Nugiel DA,Vidwans A,Etzkorn AM,Rossi KA,Benfield PA,Burton CR,Cox S,Doleniak D,Seitz SP

更新日期：2002-11-21 00:00:00

abstract：:The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested f...

journal_title：Journal of medicinal chemistry

authors： Ekström B,Ovesson M,Pring BG

更新日期：1975-11-01 00:00:00

abstract：:A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Ch...

journal_title：Journal of medicinal chemistry

authors： Anelli PL,Lattuada L,Lorusso V,Lux G,Morisetti A,Morosini P,Serleti M,Uggeri F

更新日期：2004-07-01 00:00:00

abstract：:Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is a serine/threonine kinase implicated in the regulation of many biological processes. A fragment-based lead discovery approach was used to generate potent and selective MAP4K4 inhibitors. The fragment hit pursued in this article had excellent ligand ef...

journal_title：Journal of medicinal chemistry

authors： Crawford TD,Ndubaku CO,Chen H,Boggs JW,Bravo BJ,Delatorre K,Giannetti AM,Gould SE,Harris SF,Magnuson SR,McNamara E,Murray LJ,Nonomiya J,Sambrone A,Schmidt S,Smyczek T,Stanley M,Vitorino P,Wang L,West K,Wu P,Ye W

更新日期：2014-04-24 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：:A new class of 2,3-diaziridinyl-1,4-naphthoquinone sulfonates (27 compounds) has been synthesized and evaluated as potential antineoplastic agents. The most active compounds, benzenesulfonate 4, p-toluenesulfonate 5, p-methoxybenzenesulfonate 7,8-quinolinesulfonate 17, and 2-thiophenesulfonate 20, in the aromatic sulf...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Xu SP,Zhu LY,Cosby LA,Sartorelli AC

更新日期：1989-07-01 00:00:00

abstract：:Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this se...

journal_title：Journal of medicinal chemistry

authors： Mao J,Yuan H,Wang Y,Wan B,Pieroni M,Huang Q,van Breemen RB,Kozikowski AP,Franzblau SG

更新日期：2009-11-26 00:00:00

abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

journal_title：Journal of medicinal chemistry

authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

更新日期：1991-12-01 00:00:00