Discovery of novel and long acting muscarinic acetylcholine receptor antagonists.

abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...

journal_title：Journal of medicinal chemistry

authors： Pathak U,Raza SK,Kulkarni AS,Vijayaraghvan R,Kumar P,Jaiswal DK

更新日期：2004-07-15 00:00:00

abstract：:Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N-(functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to...

journal_title：Journal of medicinal chemistry

authors： Borišek J,Vizovišek M,Sosnowski P,Turk B,Turk D,Mohar B,Novič M

更新日期：2015-09-10 00:00:00

abstract：:Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibi...

journal_title：Journal of medicinal chemistry

authors： Pearce BC,Parker RA,Deason ME,Dischino DD,Gillespie E,Qureshi AA,Volk K,Wright JJ

更新日期：1994-02-18 00:00:00

abstract：:Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radi...

journal_title：Journal of medicinal chemistry

authors： Baqi Y,Atzler K,Köse M,Glänzel M,Müller CE

更新日期：2009-06-25 00:00:00

abstract：:The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted) have been prepared, purified, and spectroscopically characterized. The water so...

journal_title：Journal of medicinal chemistry

authors： Weeks MS,Hill CL,Schinazi RF

更新日期：1992-04-03 00:00:00

abstract：:An endogenous heptadecapeptide, nociceptin/orphanin FQ (N/OFQ), and a G-protein-coupled receptor, N/OFQ peptide (NOP) receptor [or opioid-receptor-like-1 (ORL1) receptor], have been described in terms of its structure, distribution, and pharmacology. Thus, the N/OFQ and NOP receptor are located in the central nervous ...

journal_title：Journal of medicinal chemistry

authors： Hayashi S,Hirao A,Imai A,Nakamura H,Murata Y,Ohashi K,Nakata E

更新日期：2009-02-12 00:00:00

abstract：:C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of...

journal_title：Journal of medicinal chemistry

authors： Zhao H,Serby MD,Xin Z,Szczepankiewicz BG,Liu M,Kosogof C,Liu B,Nelson LT,Johnson EF,Wang S,Pederson T,Gum RJ,Clampit JE,Haasch DL,Abad-Zapatero C,Fry EH,Rondinone C,Trevillyan JM,Sham HL,Liu G

更新日期：2006-07-27 00:00:00

abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...

journal_title：Journal of medicinal chemistry

authors： Kelley JL,Koble CS,Davis RG,McLean EW,Soroko FE,Cooper BR

更新日期：1995-09-29 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. O...

journal_title：Journal of medicinal chemistry

authors： Dhar TG,Shen Z,Guo J,Liu C,Watterson SH,Gu HH,Pitts WJ,Fleener CA,Rouleau KA,Sherbina NZ,McIntyre KW,Shuster DJ,Witmer MR,Tredup JA,Chen BC,Zhao R,Bednarz MS,Cheney DL,MacMaster JF,Miller LM,Berry KK,Harper TW,

更新日期：2002-05-23 00:00:00

abstract：:A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies...

journal_title：Journal of medicinal chemistry

authors： Morales P,Gómez-Cañas M,Navarro G,Hurst DP,Carrillo-Salinas FJ,Lagartera L,Pazos R,Goya P,Reggio PH,Guaza C,Franco R,Fernández-Ruiz J,Jagerovic N

更新日期：2016-07-28 00:00:00

abstract：:A select series of methyl ether derivatives of vancomcyin aglycon were prepared and examined for antimicrobial activity against vancomycin-sensitive Staphylococcus aureus and vancomycin-resistant Enterococci faecalis as well as their binding affinity for D-Ala-D-Ala and D-Ala-D-Lac. The intent of the study was to eluc...

journal_title：Journal of medicinal chemistry

authors： Crane CM,Pierce JG,Leung SS,Tirado-Rives J,Jorgensen WL,Boger DL

更新日期：2010-10-14 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

abstract：:A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds...

journal_title：Journal of medicinal chemistry

authors： Mantri M,de Graaf O,van Veldhoven J,Göblyös A,von Frijtag Drabbe Künzel JK,Mulder-Krieger T,Link R,de Vries H,Beukers MW,Brussee J,Ijzerman AP

更新日期：2008-08-14 00:00:00

abstract：:A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent ...

journal_title：Journal of medicinal chemistry

authors： Li Y,Sun L,Yang T,Jiao W,Tang J,Huang X,Huang Z,Meng Y,Luo L,Wang X,Bian X,Zhang F,Wang K,Sun Q

更新日期：2019-01-10 00:00:00

abstract：:Prealbumin is a major thyroxine binding protein in blood that has been well studied crystallographically and has also been proposed as a model for the thyroxine nuclear receptor in tissue. The high-affinity T4 binding site in prealbumin gave a linear plot on Scatchard analysis. The interactions of selected polychlorin...

journal_title：Journal of medicinal chemistry

authors： Rickenbacher U,McKinney JD,Oatley SJ,Blake CC

更新日期：1986-05-01 00:00:00

abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...

journal_title：Journal of medicinal chemistry

authors： Singh P,Kaur S,Kaur J,Singh G,Bhatti R

更新日期：2016-04-28 00:00:00

abstract：:Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroide...

journal_title：Journal of medicinal chemistry

authors： Bochis RJ,Olen LE,Waksmunski FS,Mrozik H,Eskola P,Kulsa P,Wilks G,Taylor JE,Egerton JR,Ostlind DA,Olson G

更新日期：1981-12-01 00:00:00

abstract：:Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized ...

journal_title：Journal of medicinal chemistry

authors： Caglič D,Krutein MC,Bompiani KM,Barlow DJ,Benoni G,Pelletier JC,Reitz AB,Lairson LL,Houseknecht KL,Smith GR,Dickerson TJ

更新日期：2014-02-13 00:00:00

abstract：:Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural ...

journal_title：Journal of medicinal chemistry

authors： Yang S,Li X,Hu F,Li Y,Yang Y,Yan J,Kuang C,Yang Q

更新日期：2013-11-14 00:00:00

abstract：:A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...

journal_title：Journal of medicinal chemistry

authors： Jiang JB,Johnson MG,Defauw JM,Beine TM,Ballas LM,Janzen WP,Loomis CR,Seldin J,Cofield D,Adams L

更新日期：1992-11-13 00:00:00

abstract：:We present an analysis of the chemical fragments from lead-like ligands in the Protein Data Bank (PDB) that form hydrogen bonds to the side chains of Asp, Glu, Arg, and His, which are the most common residues found in ligand binding sites. A fragment is defined as the largest ring assembly containing the atoms involve...

journal_title：Journal of medicinal chemistry

authors： Chan AW,Laskowski RA,Selwood DL

更新日期：2010-04-22 00:00:00

abstract：:We report, for the first time, the biological activities of four-carbon-atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthetase (FPGS) as well as antitumor activity. Extension of the bridge homologation studies of classical two-carbon bridged a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Zeng Y,McGuire JJ,Kisliuk RL

更新日期：2005-08-11 00:00:00

abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

journal_title：Journal of medicinal chemistry

authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

更新日期：1981-05-01 00:00:00

abstract：:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds...

journal_title：Journal of medicinal chemistry

authors： Greenbaum DC,Mackey Z,Hansell E,Doyle P,Gut J,Caffrey CR,Lehrman J,Rosenthal PJ,McKerrow JH,Chibale K

更新日期：2004-06-03 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their des...

journal_title：Journal of medicinal chemistry

authors： Heidtmann CV,Voukia F,Hansen LN,Sørensen SH,Urlund B,Nielsen S,Pedersen M,Kelawi N,Andersen BN,Pedersen M,Reinholdt P,Kongsted J,Nielsen CU,Klitgaard JK,Nielsen P

更新日期：2020-12-24 00:00:00

abstract：:Cancer cell targeting peptides have emerged as a highly efficient approach for selective delivery of chemotherapeutics and diagnostics to different cancer cells. However, the use of α-peptides in pharmaceutical applications is hindered by their enzymatic degradation and low bioavailability. Starting with a 10-mer α-pe...

journal_title：Journal of medicinal chemistry

authors： Soudy R,Gill A,Sprules T,Lavasanifar A,Kaur K

更新日期：2011-11-10 00:00:00

abstract：:A variety of sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. Several studies have shown that they exert this effect in part by inhibiting the activation of the transcription factor NF-kappaB. In the present study we elaborated on the investigation of a data set of 103 structurally diverse...

journal_title：Journal of medicinal chemistry

authors： Wagner S,Hofmann A,Siedle B,Terfloth L,Merfort I,Gasteiger J

更新日期：2006-04-06 00:00:00

abstract：:Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5-(4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the recept...

journal_title：Journal of medicinal chemistry

authors： Zablocki JA,Miyano M,Garland RB,Pireh D,Schretzman L,Rao SN,Lindmark RJ,Panzer-Knodle SG,Nicholson NS,Taite BB

更新日期：1993-06-25 00:00:00