Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization.

abstract：:Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine residues, a process that involves a conserved tryptophan-proline-aspartate (WPD) loop in catalysis. In previously determined structures of PTPs, the WPD-loop has been observed in either an "open" conformation or a "closed" conformation. In...

journal_title：Journal of medicinal chemistry

authors： Sheriff S,Beno BR,Zhai W,Kostich WA,McDonnell PA,Kish K,Goldfarb V,Gao M,Kiefer SE,Yanchunas J,Huang Y,Shi S,Zhu S,Dzierba C,Bronson J,Macor JE,Appiah KK,Westphal RS,O'Connell J,Gerritz SW

更新日期：2011-10-13 00:00:00

abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...

journal_title：Journal of medicinal chemistry

authors： Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt EL

更新日期：1981-11-01 00:00:00

abstract：:Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered cli...

journal_title：Journal of medicinal chemistry

authors： Röhrig UF,Majjigapu SR,Vogel P,Zoete V,Michielin O

更新日期：2015-12-24 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

abstract：:A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food in...

journal_title：Journal of medicinal chemistry

authors： Mayer JP,Hsiung HM,Flora DB,Edwards P,Smith DP,Zhang XY,Gadski RA,Heiman ML,Hertel JL,Emmerson PJ,Husain S,O'brien TP,Kahl SD,Smiley DL,Zhang L,Dimarchi RD,Yan LZ

更新日期：2005-05-05 00:00:00

abstract：:In a search for improved multiple drug resistance (MDR) modulators, we identified a novel series of substituted pyrroloquinolines that selectively inhibits the function of P-glycoprotein (Pgp) without modulating multidrug resistance-related protein 1 (MRP1). These compounds were evaluated for their toxicity toward dru...

journal_title：Journal of medicinal chemistry

authors： Lee BD,Li Z,French KJ,Zhuang Y,Xia Z,Smith CD

更新日期：2004-03-11 00:00:00

abstract：:Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...

journal_title：Journal of medicinal chemistry

authors： Recanatini M,Cabrelle C

更新日期：2020-08-27 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：: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：:Peroxisome proliferator-activated receptor gamma (PPARgamma) is well-known as the receptor of thiazolidinedione antidiabetic drugs. In this paper, we present a successful example of employing structure-based virtual screening, a method that combines shape-based database search with a docking study and analogue search,...

journal_title：Journal of medicinal chemistry

authors： Lu IL,Huang CF,Peng YH,Lin YT,Hsieh HP,Chen CT,Lien TW,Lee HJ,Mahindroo N,Prakash E,Yueh A,Chen HY,Goparaju CM,Chen X,Liao CC,Chao YS,Hsu JT,Wu SY

更新日期：2006-05-04 00:00:00

abstract：:Inhibitors of the PI3-kinase/AKT (protein kinase B) pathway are under investigation as anticancer and antiviral agents. The benzimidazole derivative AKT inhibitor-IV (ChemBridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. To probe its biological activity, we synthesized AKT inh...

journal_title：Journal of medicinal chemistry

authors： Sun Q,Wu R,Cai S,Lin Y,Sellers L,Sakamoto K,He B,Peterson BR

更新日期：2011-03-10 00:00:00

abstract：:A codrug of the anti-Alzheimer drug tacrine and the natural product silibinin was synthesized. The codrug's biological and pharmacological properties were compared to an equimolar mixture of the components. The compound showed potent acetyl- and butyrylcholinesterase inhibition. In a cellular hepatotoxicity model, ana...

journal_title：Journal of medicinal chemistry

authors： Chen X,Zenger K,Lupp A,Kling B,Heilmann J,Fleck C,Kraus B,Decker M

更新日期：2012-06-14 00:00:00

abstract：:We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-su...

journal_title：Journal of medicinal chemistry

authors： Ohmori J,Kubota H,Shimizu-Sasamata M,Okada M,Sakamoto S

更新日期：1996-03-15 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：:(6R,6S)-5,8,10-Trideaza-5,6,7,8-tetrahydropteroic acid was synthesized in several steps from 4,4-(ethylenedioxy)-cyclohexanone and [4-(tert-butyloxycarbonyl)benzyl]triphenylphosphonium bromide and was elaborated to (6R,6S)-5,8,10-trideaza-5,6,7,8-tetrahydropteroyl-L-glutamic acid and (6R,6S)-5,8,10-trideaza-5,6,7,8-te...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Moran RG

更新日期：1989-03-01 00:00:00

abstract：:Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme homologous to renin. Crystal structures of inhibitor-bound complexes have provided invaluable insight regarding the three-dimensional structure of the aspartic proteinase family of enzymes, as well as the steric and polar interactions that ...

journal_title：Journal of medicinal chemistry

authors： Lunney EA,Hamilton HW,Hodges JC,Kaltenbronn JS,Repine JT,Badasso M,Cooper JB,Dealwis C,Wallace BA,Lowther WT

更新日期：1993-11-26 00:00:00

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:HIV-1 replication has been inhibited by using a compound able to target the human cellular cofactor DEAD-box ATPase DDX3, essential for HIV-1 RNA nuclear export. This compound, identified by means of a computational protocol based on pharmacophoric modeling and molecular docking calculations, represents the first smal...

journal_title：Journal of medicinal chemistry

authors： Maga G,Falchi F,Garbelli A,Belfiore A,Witvrouw M,Manetti F,Botta M

更新日期：2008-11-13 00:00:00

abstract：:Sansalvamide A, a cyclic depsipeptide isolated from a marine fungus of the genus Fusarium, is composed of four hydrophobic amino acids (Phe, two Leu, Val) and one hydroxy acid ((S)-2-hydroxy-4-methylpentanoic acid; O-Leu) with five stereogenic centers all having S-stereochemistry. We have recently synthesized the corr...

journal_title：Journal of medicinal chemistry

authors： Liu S,Gu W,Lo D,Ding XZ,Ujiki M,Adrian TE,Soff GA,Silverman RB

更新日期：2005-05-19 00:00:00

abstract：:Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound als...

journal_title：Journal of medicinal chemistry

authors： Su DS,Lim JJ,Tinney E,Wan BL,Young MB,Anderson KD,Rudd D,Munshi V,Bahnck C,Felock PJ,Lu M,Lai MT,Touch S,Moyer G,DiStefano DJ,Flynn JA,Liang Y,Sanchez R,Perlow-Poehnelt R,Miller M,Vacca JP,Williams TM,Anthony

更新日期：2009-11-26 00:00:00

abstract：:Fifteen quinolizidine derivatives have been tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. All compounds exhibited from moderate to high antiarrhythmic activity, and five of them (3, 4, 6, 13, and 15) were more active ...

journal_title：Journal of medicinal chemistry

authors： Tasso B,Budriesi R,Vazzana I,Ioan P,Micucci M,Novelli F,Tonelli M,Sparatore A,Chiarini A,Sparatore F

更新日期：2010-06-24 00:00:00

abstract：:The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothio...

journal_title：Journal of medicinal chemistry

authors： Showalter HD,Angelo MM,Berman EM,Kanter GD,Ortwine DF,Ross-Kesten SG,Sercel AD,Turner WR,Werbel LM,Worth DF

更新日期：1988-08-01 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：:A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophysical Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, additional single mutations are then added at pos...

journal_title：Journal of medicinal chemistry

authors： Zhukov A,Andrews SP,Errey JC,Robertson N,Tehan B,Mason JS,Marshall FH,Weir M,Congreve M

更新日期：2011-07-14 00:00:00

abstract：:Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activitie...

journal_title：Journal of medicinal chemistry

authors： Chen Z,Wu Y,Liu Y,Yang S,Chen Y,Lai L

更新日期：2011-05-26 00:00:00

abstract：:Dihydrocodeinone oxime (1) under Beckmann rearrangement conditions gave a product (2) that facilitated the preparation of (-)-11 alpha-substituted 1,2,3,4,5,6-hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines, a hitherto little-examined series of morphine partial structures. Compounds 7a and 12 gave good l...

journal_title：Journal of medicinal chemistry

authors： Cittern PA,Kapoor VK,Parfitt RT

更新日期：1986-10-01 00:00:00

abstract：:Anaplastic lymphoma kinase (ALK) is a valid target for anticancer therapy; however, potent ALK inhibitors suitable for clinical use are lacking. Because the majority of described kinase inhibitors bind in the ATP pocket of the kinase domain, we have characterized this pocket in ALK using site-directed mutagenesis, inh...

journal_title：Journal of medicinal chemistry

authors： Gunby RH,Ahmed S,Sottocornola R,Gasser M,Redaelli S,Mologni L,Tartari CJ,Belloni V,Gambacorti-Passerini C,Scapozza L

更新日期：2006-09-21 00:00:00

abstract：:Overexpression of the HER2 receptor is observed in about 30% of breast and ovarian cancers and is often associated with an unfavorable prognosis. We have recently designed an anti-HER2 peptide (AHNP) based on the structure of the CDR-H3 loop of the anti-HER2 rhumAb 4D5 and showed that this peptide can mimic some funct...

journal_title：Journal of medicinal chemistry

authors： Berezov A,Zhang HT,Greene MI,Murali R

更新日期：2001-08-02 00:00:00

abstract：:Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoi...

journal_title：Journal of medicinal chemistry

authors： Hilpert K,Ackermann J,Banner DW,Gast A,Gubernator K,Hadváry P,Labler L,Müller K,Schmid G,Tschopp TB

更新日期：1994-11-11 00:00:00

abstract：:Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6, ...

journal_title：Journal of medicinal chemistry

authors： Fisher MJ,Arfstan AE,Giese U,Gunn BP,Harms CS,Khau V,Kinnick MD,Lindstrom TD,Martinelli MJ,Mest HJ,Mohr M,Morin JM Jr,Mullaney JT,Nunes A,Paal M,Rapp A,Rühter G,Ruterbories KJ,Sall DJ,Scarborough RM,Schotten T,S

更新日期：1999-11-18 00:00:00