Synthesis and antisecretory and antiulcer activities of derivatives and analogues of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide.

abstract：:Several 1,2-dihydro-5-(substituted phenyl)-2(1H)-pyridinones were synthesized and evaluated for inotropic activity. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitrile (5a) and the corresponding unsubstituted analogue 14a were the most potent positive inotropic agents in this series. Alth...

journal_title：Journal of medicinal chemistry

authors： Sircar I,Duell BL,Bristol JA,Weishaar RE,Evans DB

更新日期：1987-06-01 00:00:00

abstract：:In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (MMP-2 IC(50) = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structu...

journal_title：Journal of medicinal chemistry

authors： Cherney RJ,Mo R,Meyer DT,Hardman KD,Liu RQ,Covington MB,Qian M,Wasserman ZR,Christ DD,Trzaskos JM,Newton RC,Decicco CP

更新日期：2004-06-03 00:00:00

abstract：:Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...

journal_title：Journal of medicinal chemistry

authors： Qu W,Kung MP,Hou C,Oya S,Kung HF

更新日期：2007-07-12 00:00:00

abstract：:A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Abeta plaques. 6-Ethylthio- (12h), 6-cyano- (12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI < 10...

journal_title：Journal of medicinal chemistry

authors： Cai L,Cuevas J,Temme S,Herman MM,Dagostin C,Widdowson DA,Innis RB,Pike VW

更新日期：2007-09-20 00:00:00

abstract：:Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands ...

journal_title：Journal of medicinal chemistry

authors： Cami-Kobeci G,Neal AP,Bradbury FA,Purington LC,Aceto MD,Harris LS,Lewis JW,Traynor JR,Husbands SM

更新日期：2009-03-26 00:00:00

abstract：:The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

journal_title：Journal of medicinal chemistry

authors： Kumari S,Carmona AV,Tiwari AK,Trippier PC

更新日期：2020-11-12 00:00:00

abstract：:A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3'-diethyl-9-methylthiac...

journal_title：Journal of medicinal chemistry

authors： Chang E,Congdon EE,Honson NS,Duff KE,Kuret J

更新日期：2009-06-11 00:00:00

abstract：:The endocannabinoid system consists of two cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL). In the present study, virtual screening of MGL inhibitor...

journal_title：Journal of medicinal chemistry

authors： Saario SM,Poso A,Juvonen RO,Järvinen T,Salo-Ahen OM

更新日期：2006-07-27 00:00:00

abstract：:A four-step synthesis of 2-chlorodopamine (2b) is presented as well as methods for the syntheses of the N-methyl, ethyl, and n-propyl analogues (2c-e). Compounds 2b and 2c were essentially equipotent to dopamine for increasing renal blood flow in anesthetized dogs that had been treated with the alpha-adrenergic antago...

journal_title：Journal of medicinal chemistry

authors： McCarthy JR,McCowan J,Zimmerman MB,Wenger MA,Emmert LW

更新日期：1986-09-01 00:00:00

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 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：:A computational chemistry study has been performed on a series of tetrahydropyrimidine-2-ones (THPs) as HIV-1 protease (HIV-1 PR) inhibitors. The present investigation focuses on the correlation of inhibitor-enzyme complexation energies (E(compl)), inhibitor solvation energies E(solv)[I], and both polar and nonpolar b...

journal_title：Journal of medicinal chemistry

authors： Nair AC,Jayatilleke P,Wang X,Miertus S,Welsh WJ

更新日期：2002-02-14 00:00:00

abstract：:Although the illness malaria is caused by the asexual blood stages, the presence of gametocytes is directly responsible for the infection of the vector Anopheles, thus perpetuating the plasmodial cycle. Fight against malaria is more than ever a current problem, and the solution will probably go through the development...

journal_title：Journal of medicinal chemistry

authors： Dechy-Cabaret O,Benoit-Vical F

更新日期：2012-12-13 00:00:00

abstract：:As a receptor tyrosine kinase of insulin receptor (IR) subfamily, anaplastic lymphoma kinase (ALK) has been validated to play important roles in various cancers, especially anaplastic large cell lymphoma (ALCL), nonsmall cell lung cancer (NSCLC), and neuroblastomas. Currently, five small-molecule inhibitors of ALK, in...

journal_title：Journal of medicinal chemistry

authors： Kong X,Pan P,Sun H,Xia H,Wang X,Li Y,Hou T

更新日期：2019-12-26 00:00:00

abstract：:A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expr...

journal_title：Journal of medicinal chemistry

authors： Tafesse L,Kanemasa T,Kurose N,Yu J,Asaki T,Wu G,Iwamoto Y,Yamaguchi Y,Ni C,Engel J,Tsuno N,Patel A,Zhou X,Shintani T,Brown K,Hasegawa T,Shet M,Iso Y,Kato A,Kyle DJ

更新日期：2014-08-14 00:00:00

abstract：:Most bromodomain inhibitors mimic the interactions of the natural acetylated lysine (KAc) histone substrate through key interactions with conserved asparagine and tyrosine residues within the binding pocket. Herein we report the optimization of a series of phenyl sulfonamides that exhibit a novel mode of binding to no...

journal_title：Journal of medicinal chemistry

authors： Lucas SCC,Atkinson SJ,Bamborough P,Barnett H,Chung CW,Gordon L,Mitchell DJ,Phillipou A,Prinjha RK,Sheppard RJ,Tomkinson NCO,Watson RJ,Demont EH

更新日期：2020-05-28 00:00:00

abstract：:A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacological hypothesis that NOP partial agonists would afford a dual pharmacological action of attenuating Parkinson's disease (PD) motor symptoms and development of levodopa-induce...

journal_title：Journal of medicinal chemistry

authors： Kamakolanu UG,Meyer ME,Yasuda D,Polgar WE,Marti M,Mercatelli D,Pisanò CA,Brugnoli A,Morari M,Zaveri NT

更新日期：2020-03-12 00:00:00

abstract：:The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly...

journal_title：Journal of medicinal chemistry

authors： Quiñones-Torrelo C,Sagrado S,Villanueva-Camañas RM,Medina-Hernández MJ

更新日期：1999-08-12 00:00:00

abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Remers WA,Catino JJ

更新日期：1989-08-01 00:00:00

abstract：:A series of 1-R-5-alkoxy-3H-1,4-benzodiazepin-2(1H)-ones was prepared and evaluated for central nervous system depressant activity. Several of these compounds, in particular, 7-chloro-5-ethoxy-1-methyl-3H-1,4-benzodiazepin-2(1H)-one (2), gave a profile and activity level similar to diazepam when measured in mice. ...

journal_title：Journal of medicinal chemistry

authors： Gogerty JH,Griot RG,Habeck D,Iorio LC,Houlihan WJ

更新日期：1977-07-01 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：: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：:N-(R)- and N-(S)-lactylsphingosine and their corresponding dihydrosphingosine derivatives were synthesized. The antileukemic activities of these compounds were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in human leukemia HL-60 cells. N-(R)- and N-(S)-Lactylsphingosine disp...

journal_title：Journal of medicinal chemistry

authors： Azuma H,Takao R,Shikata K,Niiro H,Tachibana T,Ogino K

更新日期：2003-07-31 00:00:00

abstract：:A GABA(A) receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-norallopregnanolone (i.e., 3alpha-hydroxy-7-nor-5alpha-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons ...

journal_title：Journal of medicinal chemistry

authors： Suñol C,García DA,Bujons J,Kristofíková Z,Matyás L,Babot Z,Kasal A

更新日期：2006-06-01 00:00:00

abstract：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...

journal_title：Journal of medicinal chemistry

authors： Becker JW,Rotonda J,Soisson SM,Aspiotis R,Bayly C,Francoeur S,Gallant M,Garcia-Calvo M,Giroux A,Grimm E,Han Y,McKay D,Nicholson DW,Peterson E,Renaud J,Roy S,Thornberry N,Zamboni R

更新日期：2004-05-06 00:00:00

abstract：:A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocryst...

journal_title：Journal of medicinal chemistry

authors： Bryan MC,Drobnick J,Gobbi A,Kolesnikov A,Chen Y,Rajapaksa N,Ndubaku C,Feng J,Chang W,Francis R,Yu C,Choo EF,DeMent K,Ran Y,An L,Emson C,Huang Z,Sujatha-Bhaskar S,Brightbill H,DiPasquale A,Maher J,Wai J,McKenzi

更新日期：2019-07-11 00:00:00

abstract：:A series of alpha,alpha-diaryl-1-piperidinebutanols was evaluated for antiarrhythmic activity in the coronary ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group yielded compounds with the best antiarrhythmic profiles in this series. The length of the methylene ch...

journal_title：Journal of medicinal chemistry

authors： Hoefle ML,Blouin LT,Fleming RW,Hastings S,Hinkley JM,Mertz TE,Steffe TJ,Stratton CS

更新日期：1991-01-01 00:00:00

abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...

journal_title：Journal of medicinal chemistry

authors： Doll MK,Nichols DE,Kilts JD,Prioleau C,Lawler CP,Lewis MM,Mailman RB

更新日期：1999-03-11 00:00:00

abstract：:Proteins which bind methylated lysines ("readers" of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a re...

journal_title：Journal of medicinal chemistry

authors： Herold JM,Wigle TJ,Norris JL,Lam R,Korboukh VK,Gao C,Ingerman LA,Kireev DB,Senisterra G,Vedadi M,Tripathy A,Brown PJ,Arrowsmith CH,Jin J,Janzen WP,Frye SV

更新日期：2011-04-14 00:00:00

abstract：:The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin as...

journal_title：Journal of medicinal chemistry

authors： Andreani A,Granaiola M,Locatelli A,Morigi R,Rambaldi M,Varoli L,Calonghi N,Cappadone C,Farruggia G,Stefanelli C,Masotti L,Nguyen TL,Hamel E,Shoemaker RH

更新日期：2012-03-08 00:00:00