Isosorbide-2-benzyl carbamate-5-salicylate, a peripheral anionic site binding subnanomolar selective butyrylcholinesterase inhibitor.

abstract：:To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecul...

journal_title：Journal of medicinal chemistry

authors： Tafi A,Bernardini C,Botta M,Corelli F,Andreini M,Martinelli A,Ortore G,Baraldi PG,Fruttarolo F,Borea PA,Tuccinardi T

更新日期：2006-07-13 00:00:00

abstract：:Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...

journal_title：Journal of medicinal chemistry

authors： Fliri AF,Loging WT,Thadeio PF,Volkmann RA

更新日期：2005-11-03 00:00:00

abstract：:Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine...

journal_title：Journal of medicinal chemistry

authors： Chwang TL,Wood WF,Parkhurst JR,Nesnow S,Danenberg PV,Heidelberger C

更新日期：1976-05-01 00:00:00

abstract：:Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with lo...

journal_title：Journal of medicinal chemistry

authors： Heikkilä T,Ramsey C,Davies M,Galtier C,Stead AM,Johnson AP,Fishwick CW,Boa AN,McConkey GA

更新日期：2007-01-25 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：:Novel, lipophilic cycloSal triesters 4a-c and 5a-c were synthesized, respectively, from the ara- and ribo-configurated 2'-fluorinated-2', 3'-dideoxyadenosines 2 and 3. The cycloSal phosphotriesters were used as tools to study the effects of the two different sugar pucker conformations induced by two opposite configura...

journal_title：Journal of medicinal chemistry

authors： Meier C,Knispel T,Marquez VE,Siddiqui MA,De Clercq E,Balzarini J

更新日期：1999-05-06 00:00:00

abstract：:The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe w...

journal_title：Journal of medicinal chemistry

authors： Wright JE,Hayes MJ,Subramanyam V,Soloway AH

更新日期：1977-12-01 00:00:00

abstract：:Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that t...

journal_title：Journal of medicinal chemistry

authors： Ghosh AK,Lee HY,Thompson WJ,Culberson C,Holloway MK,McKee SP,Munson PM,Duong TT,Smith AM,Darke PL

更新日期：1994-04-15 00:00:00

abstract：:The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocycli...

journal_title：Journal of medicinal chemistry

authors： Woltersdorf OW Jr,deSolms SJ,Schultz EM,Cragoe EJ Jr

更新日期：1977-11-01 00:00:00

abstract：:Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto-enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding m...

journal_title：Journal of medicinal chemistry

authors： Xiao Z,Chen D,Song S,van der Vlag R,van der Wouden PE,van Merkerk R,Cool RH,Hirsch AKH,Melgert BN,Quax WJ,Poelarends GJ,Dekker FJ

更新日期：2020-10-22 00:00:00

abstract：:Gene therapy based on gene delivery is a promising strategy for the treatment of human disease. Here we present data on structure/biological activity of new biodegradable cholesterol-based cationic lipids with various heterocyclic cationic head groups and linker types. Enhanced accumulation of nucleic acids in the cel...

journal_title：Journal of medicinal chemistry

authors： Medvedeva DA,Maslov MA,Serikov RN,Morozova NG,Serebrenikova GA,Sheglov DV,Latyshev AV,Vlassov VV,Zenkova MA

更新日期：2009-11-12 00:00:00

abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Chaillet P,Soroca-Lucas E,Marçais-Collado H,Costentin J,Roques BP

更新日期：1983-01-01 00:00:00

abstract：:10-Acetyl-7,8-dihydroxyxantho[2,3-f]tetralin is obtained by photo-Fries rearrangement of an acylated and double ketal protected tetralin followed by sodium thiocresylate catalyzed rearrangement of the resulting benzoyltetralin. Introduction of the 10-hydroxy function with base, triethyl phosphite, and molecular oxygen...

journal_title：Journal of medicinal chemistry

authors： Lown JW,Sondhi SM,Plambeck JA

更新日期：1986-11-01 00:00:00

abstract：:Fragment-based drug discovery has become a powerful method for the generation of drug leads against therapeutic targets. Beyond the identification of novel and effective starting points for drug design, fragments have emerged as reliable tools for assessing protein druggability and identifying protein hot spots. Here,...

journal_title：Journal of medicinal chemistry

authors： Krimm I,Lancelin JM,Praly JP

更新日期：2012-02-09 00:00:00

abstract：:A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purifie...

journal_title：Journal of medicinal chemistry

authors： Neamati N,Turpin JA,Winslow HE,Christensen JL,Williamson K,Orr A,Rice WG,Pommier Y,Garofalo A,Brizzi A,Campiani G,Fiorini I,Nacci V

更新日期：1999-08-26 00:00:00

abstract：:New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-r...

journal_title：Journal of medicinal chemistry

authors： Beltramo M,Robert V,Galibert M,Madinier JB,Marceau P,Dardente H,Decourt C,De Roux N,Lomet D,Delmas AF,Caraty A,Aucagne V

更新日期：2015-04-23 00:00:00

abstract：:Multidrug-resistant Staphylococcus aureus, including MRSA (methicillin-resistant) and VRSA (vancomycin-resistant), causes serious healthcare-associated infections, even sepsis and death. Here, we identified six novel cathelicidins (CATHPb1-6) from Python bivittatu, and CATHPb1 displayed the best in vitro pharmacologic...

journal_title：Journal of medicinal chemistry

authors： Cai S,Qiao X,Feng L,Shi N,Wang H,Yang H,Guo Z,Wang M,Chen Y,Wang Y,Yu H

更新日期：2018-03-08 00:00:00

abstract：:The bioavailability of aromatic azaheterocyclic drugs can be affected by the activity of aldehyde oxidase (AO). Susceptibility to AO metabolism is difficult to predict computationally and can be complicated in vivo by differences between species. Here we report the use of bis(((difluoromethyl)sulfinyl)oxy)zinc (DFMS) ...

journal_title：Journal of medicinal chemistry

authors： O'Hara F,Burns AC,Collins MR,Dalvie D,Ornelas MA,Vaz AD,Fujiwara Y,Baran PS

更新日期：2014-02-27 00:00:00

abstract：:With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared. 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione. Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazol...

journal_title：Journal of medicinal chemistry

authors： Renault J,Giorgi-Renault S,Baron M,Mailliet P,Paoletti C,Cros S,Voisin E

更新日期：1983-12-01 00:00:00

abstract：:In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bou...

journal_title：Journal of medicinal chemistry

authors： Hu X,Compton JR,Abdulhameed MD,Marchand CL,Robertson KL,Leary DH,Jadhav A,Hershfield JR,Wallqvist A,Friedlander AM,Legler PM

更新日期：2013-07-11 00:00:00

abstract：:A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituen...

journal_title：Journal of medicinal chemistry

authors： Hodges JC,Remers WA,Bradner WT

更新日期：1981-10-01 00:00:00

abstract：:A series of N-benzylpiperidine benzisoxazoles has been developed as potent and selective inhibitors of the enzyme acetylcholinesterase (AChE). The benzisoxazole heterocycle was found to be an appropriate bioisosteric replacement for the benzoyl functionality present in the N-benzylpiperidine class of inhibitors. The t...

journal_title：Journal of medicinal chemistry

authors： Villalobos A,Blake JF,Biggers CK,Butler TW,Chapin DS,Chen YL,Ives JL,Jones SB,Liston DR,Nagel AA

更新日期：1994-08-19 00:00:00

abstract：:The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antid...

journal_title：Journal of medicinal chemistry

authors： Chao B,Tong XK,Tang W,Li DW,He PL,Garcia JM,Zeng LM,Gao AH,Yang L,Li J,Nan FJ,Jacobs M,Altmeyer R,Zuo JP,Hu YH

更新日期：2012-04-12 00:00:00

abstract：:Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of he...

journal_title：Journal of medicinal chemistry

authors： Moon KY,Shirota FN,Baturay N,Kwon CH

更新日期：1995-03-03 00:00:00

abstract：:Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alter...

journal_title：Journal of medicinal chemistry

authors： Pero JE,Matthews JM,Behm DJ,Brnardic EJ,Brooks C,Budzik BW,Costell MH,Donatelli CA,Eisennagel SH,Erhard K,Fischer MC,Holt DA,Jolivette LJ,Li H,Li P,McAtee JJ,McCleland BW,Pendrak I,Posobiec LM,Rivera KLK,Rivero RA

更新日期：2018-12-27 00:00:00

abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

journal_title：Journal of medicinal chemistry

authors： Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

更新日期：2018-02-22 00:00:00

abstract：:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a...

journal_title：Journal of medicinal chemistry

authors： Fleysher MH,Bernacki RJ,Bullard GA

更新日期：1980-12-01 00:00:00

abstract：:Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to p...

journal_title：Journal of medicinal chemistry

authors： Khadem HS,Swartz DL,Cermak RC

更新日期：1977-07-01 00:00:00

abstract：:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active aga...

journal_title：Journal of medicinal chemistry

authors： Bolognese A,Correale G,Manfra M,Lavecchia A,Novellino E,Pepe S

更新日期：2006-08-24 00:00:00

abstract：:In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable f...

journal_title：Journal of medicinal chemistry

authors： Pemberton N,Mogemark M,Arlbrandt S,Bold P,Cox RJ,Gardelli C,Holden NS,Karabelas K,Karlsson J,Lever S,Li X,Lindmark H,Norberg M,Perry MWD,Petersen J,Rodrigo Blomqvist S,Thomas M,Tyrchan C,Westin Eriksson A,Zlatoidsky

更新日期：2018-06-28 00:00:00