Facile N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the flavin-containing monooxygenase. A convenient synthesis of tritiated [methyl-3H]-4-phenyl-2,3-dihydropyridinium species.

abstract：:Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles. Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dime...

journal_title：Journal of medicinal chemistry

authors： Sarges R,Howard HR,Koe BK,Weissman A

更新日期：1989-02-01 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：: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

abstract：:For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which in...

journal_title：Journal of medicinal chemistry

authors： Neyts J,De Clercq E,Singha R,Chang YH,Das AR,Chakraborty SK,Hong SC,Tsay SC,Hsu MH,Hwu JR

更新日期：2009-03-12 00:00:00

abstract：:The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The overexpression of MMP-3 (stromelysin-1) and MMP-13 (collagenase-3) is associated with nonhealing wounds, whereas active...

journal_title：Journal of medicinal chemistry

authors： Fray MJ,Dickinson RP,Huggins JP,Occleston NL

更新日期：2003-07-31 00:00:00

abstract：:Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...

journal_title：Journal of medicinal chemistry

authors： Tamura R,Balabanova A,Frakes SA,Bargmann A,Grimm J,Koch TH,Yin H

更新日期：2019-02-28 00:00:00

abstract：:High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identify...

journal_title：Journal of medicinal chemistry

authors： Pike KG,Morris J,Ruston L,Pass SL,Greenwood R,Williams EJ,Demeritt J,Culshaw JD,Gill K,Pass M,Finlay MR,Good CJ,Roberts CA,Currie GS,Blades K,Eden JM,Pearson SE

更新日期：2015-03-12 00:00:00

abstract：:Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML ac...

journal_title：Journal of medicinal chemistry

authors： Sang F,Ding Y,Wang J,Sun B,Sun J,Geng Y,Zhang Z,Ding K,Wu LL,Liu JW,Bai C,Yang G,Zhang Q,Li LY,Chen Y

更新日期：2016-02-11 00:00:00

abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...

journal_title：Journal of medicinal chemistry

authors： Han QP,Dryhurst G

更新日期：1996-03-29 00:00:00

abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

journal_title：Journal of medicinal chemistry

authors： Lövgren K,Hedberg A,Nilsson JL

更新日期：1981-04-01 00:00:00

abstract：:Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly describe...

journal_title：Journal of medicinal chemistry

authors： Rankovic Z

更新日期：2017-07-27 00:00:00

abstract：:A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay...

journal_title：Journal of medicinal chemistry

authors： Bradbury RH,Allott CP,Dennis M,Fisher E,Major JS,Masek BB,Oldham AA,Pearce RJ,Rankine N,Revill JM

更新日期：1992-10-30 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：:A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor subtypes. The data indicated that a considerable degree of structural variati...

journal_title：Journal of medicinal chemistry

authors： de Costa BR,He XS,Dominguez C,Cutts J,Williams W,Bowen WD

更新日期：1994-01-21 00:00:00

abstract：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...

journal_title：Journal of medicinal chemistry

authors： Li S,Xu H,Cui S,Wu F,Zhang Y,Su M,Gong Y,Qiu S,Jiao Q,Qin C,Shan J,Zhang M,Wang J,Yin Q,Xu M,Liu X,Wang R,Zhu L,Li J,Xu Y,Jiang H,Zhao Z,Li J,Li H

更新日期：2016-07-28 00:00:00

abstract：:Multivalent ligands are promising pharmacological tools that may be more efficacious for several diseases than highly selective single-target drugs. A combined therapy using dopaminergic agonists and adenosinergic antagonists is currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda, T.; et al....

journal_title：Journal of medicinal chemistry

authors： Vendrell M,Angulo E,Casadó V,Lluis C,Franco R,Albericio F,Royo M

更新日期：2007-06-28 00:00:00

abstract：:Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity fo...

journal_title：Journal of medicinal chemistry

authors： Våbenø J,Nielsen CU,Ingebrigtsen T,Lejon T,Steffansen B,Luthman K

更新日期：2004-09-09 00:00:00

abstract：:We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterifi...

journal_title：Journal of medicinal chemistry

authors： McGuigan C,Madela K,Aljarah M,Bourdin C,Arrica M,Barrett E,Jones S,Kolykhalov A,Bleiman B,Bryant KD,Ganguly B,Gorovits E,Henson G,Hunley D,Hutchins J,Muhammad J,Obikhod A,Patti J,Walters CR,Wang J,Vernachio J,Ra

更新日期：2011-12-22 00:00:00

abstract：:Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

journal_title：Journal of medicinal chemistry

authors： Belorusova AY,Chalhoub S,Rovito D,Rochel N

更新日期：2020-09-10 00:00:00

abstract：:2-(3,4-Dichloroanilino)quinolizinium bromide (3) was prepared by reaction of 2-bromoquinolizinium bromide with 3,4-dichloroaniline in ethanol. This compound possesses unique antispasmodic, antisecretory, and antiulcerogenic properties. ...

journal_title：Journal of medicinal chemistry

authors： Alaimo RJ,Goldenberg MM

更新日期：1975-11-01 00:00:00

abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

journal_title：Journal of medicinal chemistry

authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-11-08 00:00:00

abstract：:In the treatment of cardiovascular diseases, it could be of therapeutic interest to associate the hypotensive effects resulting from the inhibition of angiotensin II formation, ensured by endothelial angiotensin-converting enzyme (ACE), with the diuretic and natriuretic responses due to the protection of the endogenou...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Coric P,Turcaud S,Rousselet N,Gonzalez W,Barbe B,Pham I,Jullian N,Michel JB,Roques BP

更新日期：1994-04-15 00:00:00

abstract：:A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinitie...

journal_title：Journal of medicinal chemistry

authors： Zhang T,Liu Y,Yang X,Martin GE,Yao H,Shang J,Bugianesi RM,Ellsworth KP,Sonatore LM,Nizner P,Sherer EC,Hill SE,Knemeyer IW,Geissler WM,Dandliker PJ,Helmy R,Wood HB

更新日期：2016-03-10 00:00:00

abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

journal_title：Journal of medicinal chemistry

authors： Kuhlmann KF,Mosher CW

更新日期：1981-11-01 00:00:00

abstract：:The sequence and configuration of amino acids in the cytostatic cyclic tetrapeptide WF-3161 are established as cyclo(L-Leu-L-Pip-L-Aoe-D-Phe) where Pip = pipecolic acid and Aoe = 2-amino-8-oxo-9,10-epoxydecanoic acid. In chloroform, WF-3161 adopts a conformation with a possible gamma-turn between Leu NH and Aoe C = O ...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Pottorf RS,Rich DH

更新日期：1986-11-01 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：:Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic t...

journal_title：Journal of medicinal chemistry

authors： Peach ML,Tan N,Choyke SJ,Giubellino A,Athauda G,Burke TR Jr,Nicklaus MC,Bottaro DP

更新日期：2009-02-26 00:00:00

abstract：:Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug sel...

journal_title：Journal of medicinal chemistry

authors： Hoffmann BR,El-Mansy MF,Sem DS,Greene AS

更新日期：2012-10-11 00:00:00

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 00:00:00