A Smart Europium-Ruthenium Complex as Anticancer Prodrug: Controllable Drug Release and Real-Time Monitoring under Different Light Excitations.

abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...

journal_title：Journal of medicinal chemistry

authors： German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

更新日期：2011-10-27 00:00:00

abstract：:A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3 alpha, 4 beta, 5 alpha)]-2-amino-1, 9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereo...

journal_title：Journal of medicinal chemistry

authors： Tino JA,Clark JM,Field AK,Jacobs GA,Lis KA,Michalik TL,McGeever-Rubin B,Slusarchyk WA,Spergel SH,Sundeen JE

更新日期：1993-04-30 00:00:00

abstract：:A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as...

journal_title：Journal of medicinal chemistry

authors： Cheung PK,Horhant D,Bandy LE,Zamiri M,Rabea SM,Karagiosov SK,Matloobi M,McArthur S,Harrigan PR,Chabot B,Grierson DS

更新日期：2016-03-10 00:00:00

abstract：:A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all ...

journal_title：Journal of medicinal chemistry

authors： Okawa T,Aramaki Y,Yamamoto M,Kobayashi T,Fukumoto S,Toyoda Y,Henta T,Hata A,Ikeda S,Kaneko M,Hoffman ID,Sang BC,Zou H,Kawamoto T

更新日期：2017-08-24 00:00:00

abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...

journal_title：Journal of medicinal chemistry

authors： Yang X,Zhong J,Zhang Q,Qian J,Song K,Ruan C,Xu J,Ding K,Zhang J

更新日期：2018-09-13 00:00:00

abstract：:A number of 1,2-benzisoxazoles, substituted in the 3 position with 4-substituted phenyl groups and in the 5--7 positions with acetic and propionic acid residues, have been synthesized and tested in the rat carrageenan foot edema assay. Activity has been found in the 6- and 7-substituted acids. ...

journal_title：Journal of medicinal chemistry

authors： Saunders JC,Williamson WR

更新日期：1979-12-01 00:00:00

abstract：:(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molec...

journal_title：Journal of medicinal chemistry

authors： Chu CK,Yadav V,Chong YH,Schinazi RF

更新日期：2005-06-16 00:00:00

abstract：:The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 overexpression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguani...

journal_title：Journal of medicinal chemistry

authors： Sharma SK,Wu Y,Steinbergs N,Crowley ML,Hanson AS,Casero RA,Woster PM

更新日期：2010-07-22 00:00:00

abstract：:HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and ev...

journal_title：Journal of medicinal chemistry

authors： Hrib NJ,Jurcak JG,Bregna DE,Burgher KL,Hartman HB,Kafka S,Kerman LL,Kongsamut S,Roehr JE,Szewczak MR,Woods-Kettelberger AT,Corbett R

更新日期：1996-09-27 00:00:00

abstract：:Acid ceramidase (AC) is an intracellular cysteine amidase that catalyzes the hydrolysis of the lipid messenger ceramide. By regulating ceramide levels in cells, AC may contribute to the regulation of cancer cell proliferation and senescence and to the response to cancer therapy. We recently identified the antitumoral ...

journal_title：Journal of medicinal chemistry

authors： Pizzirani D,Pagliuca C,Realini N,Branduardi D,Bottegoni G,Mor M,Bertozzi F,Scarpelli R,Piomelli D,Bandiera T

更新日期：2013-05-09 00:00:00

abstract：:In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane prepar...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung MP,Panyachotipun C,Prapansiri V,Foulon C,Brooks BP,Szabo SA,Tejani-Butt S,Frazer A,Kung HF

更新日期：1992-11-13 00:00:00

abstract：:With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the ...

journal_title：Journal of medicinal chemistry

authors： Yu Q,Holloway HW,Flippen-Anderson JL,Hoffman B,Brossi A,Greig NH

更新日期：2001-11-22 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied ...

journal_title：Journal of medicinal chemistry

authors： Teixeira LJ,Seabra M,Reis E,da Cruz MT,de Lima MC,Pereira E,Miranda MA,Marques MP

更新日期：2004-05-20 00:00:00

abstract：:A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component an...

journal_title：Journal of medicinal chemistry

authors： Kalra P,Reddy TV,Jayaram B

更新日期：2001-12-06 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...

journal_title：Journal of medicinal chemistry

authors： Rognan D,Boulanger T,Hoffmann R,Vercauteren DP,Andre JM,Durant F,Wermuth CG

更新日期：1992-05-29 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-tria...

journal_title：Journal of medicinal chemistry

authors： Ferreira SB,Sodero AC,Cardoso MF,Lima ES,Kaiser CR,Silva FP,Ferreira VF

更新日期：2010-03-25 00:00:00

abstract：:On the basis of a mu opioid receptor (MOR) homology model and the isosterism concept, three generations of 14-heteroaromatically substituted naltrexone derivatives were designed, synthesized, and evaluated as potential MOR-selective ligands. The first-generation ligands appeared to be MOR-selective, whereas the second...

journal_title：Journal of medicinal chemistry

authors： Yuan Y,Zaidi SA,Elbegdorj O,Aschenbach LC,Li G,Stevens DL,Scoggins KL,Dewey WL,Selley DE,Zhang Y

更新日期：2013-11-27 00:00:00

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...

journal_title：Journal of medicinal chemistry

authors： Zhao R,al-Said NH,Sternbach DL,Lown JW

更新日期：1997-01-17 00:00:00

abstract：:Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock sei...

journal_title：Journal of medicinal chemistry

authors： Cortes S,Liao ZK,Watson D,Kohn H

更新日期：1985-05-01 00:00:00

abstract：:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds ...

journal_title：Journal of medicinal chemistry

authors： Sashidhara KV,Kumar M,Khedgikar V,Kushwaha P,Modukuri RK,Kumar A,Gautam J,Singh D,Sridhar B,Trivedi R

更新日期：2013-01-10 00:00:00

abstract：:Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of...

journal_title：Journal of medicinal chemistry

authors： Shao LD,Su J,Ye B,Liu JX,Zuo ZL,Li Y,Wang YY,Xia C,Zhao QS

更新日期：2017-11-09 00:00:00

abstract：:A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at...

journal_title：Journal of medicinal chemistry

authors： Shaw DE,Baig F,Bruce I,Chamoin S,Collingwood SP,Cross S,Dayal S,Drückes P,Furet P,Furminger V,Haggart D,Hussey M,Konstantinova I,Loren JC,Molteni V,Roberts S,Reilly J,Saunders AM,Stringer R,Sviridenko L,Thomas M,

更新日期：2016-09-08 00:00:00

abstract：:Endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) is an endogenous tetrapeptide that combines potency and efficacy with high affinity and selectivity toward the μ opioid receptor, the most responsible for analgesic effects in the central nervous system. The presence of the Pro(2) represents a crucial factor for the ligand s...

journal_title：Journal of medicinal chemistry

authors： Mollica A,Pinnen F,Stefanucci A,Feliciani F,Campestre C,Mannina L,Sobolev AP,Lucente G,Davis P,Lai J,Ma SW,Porreca F,Hruby VJ

更新日期：2012-04-12 00:00:00

abstract：:Structure-based methods were used to design a potent and highly selective group II p21-activated kinase (PAK) inhibitor with a novel binding mode, compound 17. Hydrophobic interactions within a lipophilic pocket past the methionine gatekeeper of group II PAKs approached by these type I 1/2 binders were found to be imp...

journal_title：Journal of medicinal chemistry

authors： Staben ST,Feng JA,Lyle K,Belvin M,Boggs J,Burch JD,Chua CC,Cui H,DiPasquale AG,Friedman LS,Heise C,Koeppen H,Kotey A,Mintzer R,Oh A,Roberts DA,Rouge L,Rudolph J,Tam C,Wang W,Xiao Y,Young A,Zhang Y,Hoeflich K

更新日期：2014-02-13 00:00:00

abstract：:We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and sugg...

journal_title：Journal of medicinal chemistry

authors： Karlberg T,Markova N,Johansson I,Hammarström M,Schütz P,Weigelt J,Schüler H

更新日期：2010-07-22 00:00:00

abstract：:As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of "dual-prodrug" by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10-17, named Fuplatin...

journal_title：Journal of medicinal chemistry

authors： Zhang R,Song XQ,Liu RP,Ma ZY,Xu JY

更新日期：2019-05-09 00:00:00

abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

journal_title：Journal of medicinal chemistry

authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

更新日期：1977-02-01 00:00:00