4-Methyl-3-(arylsulfonyl)furoxans: a new class of potent inhibitors of platelet aggregation.

abstract：:A series of bis(hydroxymethyl)-substituted heterocycles were synthesized and converted to the corresponding bis(methylcarbamate) derivatives. The heterocyclic systems studied were based on 2-phenyl-3-methylfuran (2-4), 1-phenylpyrazole (5-7), 1-phenyl-5-methylpyrazole (9-11), 1-phenyl-5-methylthiophene (13), 1-phenyl-...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Jones AN

更新日期：1984-12-01 00:00:00

abstract：:Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4...

journal_title：Journal of medicinal chemistry

authors： Venable JD,Cai H,Chai W,Dvorak CA,Grice CA,Jablonowski JA,Shah CR,Kwok AK,Ly KS,Pio B,Wei J,Desai PJ,Jiang W,Nguyen S,Ling P,Wilson SJ,Dunford PJ,Thurmond RL,Lovenberg TW,Karlsson L,Carruthers NI,Edwards JP

更新日期：2005-12-29 00:00:00

abstract：:A diverse range of chromen-2-one, chromen-4-one and pyrimidoisoquinolin-4-one derivatives was synthesized and evaluated for inhibitory activity against the DNA repair enzyme DNA-dependent protein kinase (DNA-PK), with a view to elucidating structure-activity relationships for potency and kinase selectivity. DNA-PK inh...

journal_title：Journal of medicinal chemistry

authors： Griffin RJ,Fontana G,Golding BT,Guiard S,Hardcastle IR,Leahy JJ,Martin N,Richardson C,Rigoreau L,Stockley M,Smith GC

更新日期：2005-01-27 00:00:00

abstract：:Various 3'-deoxythymidine analogues with an heterocyclic five-membered ring in the 3'-erythro position have been synthesized. The pyrrol-1-yl (3) and the 1,2,4-triazol-4-yl (5) compounds were synthesized from 1-(3-amino-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine. The pyrazol-1-yl (16a), imidazol-1-yl (16b), and...

journal_title：Journal of medicinal chemistry

authors： Wigerinck P,Van Aerschot A,Janssen G,Claes P,Balzarini J,De Clercq E,Herdewijn P

更新日期：1990-02-01 00:00:00

abstract：:cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment. Through a type II kinase inhibitor design approach we discovered a highly potent type II cKIT kinase inhibitor compound 35 (CHMFL-KIT-8140), which potently inhibited bo...

journal_title：Journal of medicinal chemistry

authors： Li B,Wang A,Liu J,Qi Z,Liu X,Yu K,Wu H,Chen C,Hu C,Wang W,Wu J,Hu Z,Ye L,Zou F,Liu F,Wang B,Wang L,Ren T,Zhang S,Bai M,Zhang S,Liu J,Liu Q

更新日期：2016-09-22 00:00:00

abstract：:Ten analogues of the highly mu-receptor selective cyclic opioid peptide H-Tyr-D-Orn-Phe-Asp-NH2 (1) were synthesized by the solid phase method and were characterized in vitro in mu- and delta-receptor representative binding assays and bioassays. These cyclic analogues are structurally related to the linear opioid pept...

journal_title：Journal of medicinal chemistry

authors： Schiller PW,Nguyen TM,Maziak LA,Wilkes BC,Lemieux C

更新日期：1987-11-01 00:00:00

abstract：:Synthesis and biological activity of 17-esters of 6-dehydro-16-methylene-17 alpha-hydroxyprogesterone are presented. A systematic study of the influence of the alteration of halogen at 6 and the acyl group at 17 on the progestational and antiandrogenic activities of the resulting structures is described. A convenien...

journal_title：Journal of medicinal chemistry

authors： Shapiro EL,Weber L,Harris H,Miskowicz C,Neri R,Herzog HL

更新日期：1972-07-01 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：:Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effec...

journal_title：Journal of medicinal chemistry

authors： Yin QK,Wang CX,Wang YQ,Guo QL,Zhang ZL,Ou TM,Huang SL,Li D,Wang HG,Tan JH,Chen SB,Huang ZS

更新日期：2019-03-28 00:00:00

abstract：:Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...

journal_title：Journal of medicinal chemistry

authors： McDonagh AF,Lightner DA

更新日期：2007-02-08 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic...

journal_title：Journal of medicinal chemistry

authors： Lacône V,Hunault J,Pipelier M,Blot V,Lecourt T,Rocher J,Turcot-Dubois AL,Marionneau S,Douillard JY,Clément M,Le Pendu J,Bonneville M,Micouin L,Dubreuil D

更新日期：2009-08-13 00:00:00

abstract：:Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A ...

journal_title：Journal of medicinal chemistry

authors： Liu YA,Jin Q,Zou Y,Ding Q,Yan S,Wang Z,Hao X,Nguyen B,Zhang X,Pan J,Mo T,Jacobsen K,Lam T,Wu TY,Petrassi HM,Bursulaya B,DiDonato M,Gordon WP,Liu B,Baaten J,Hill R,Nguyen-Tran V,Qiu M,Zhang YQ,Kamireddy A,

更新日期：2020-03-26 00:00:00

abstract：:The cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3- pyridazinyl)-2H-indol-2-one (1, LY195115) is a potent, competitive inhibitor (Ki = 80 nM) of sarcoplasmic reticulum derived phosphodiesterase (SR-PDE). Moreover, the compound is a potent positive inotrope both in vitro and in vivo. To assist furth...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Jones ND,Krushinski JH,Pollock GD,Swartzendruber JK,Hayes JS

更新日期：1987-04-01 00:00:00

abstract：:The transcription factor nuclear factor kappaB (NF-kappaB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous ...

journal_title：Journal of medicinal chemistry

authors： Heynekamp JJ,Weber WM,Hunsaker LA,Gonzales AM,Orlando RA,Deck LM,Jagt DL

更新日期：2006-11-30 00:00:00

abstract：:The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to d...

journal_title：Journal of medicinal chemistry

authors： Singla P,Dalal P,Kaur M,Arya G,Nimesh S,Singh R,Salunke DB

更新日期：2018-11-21 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：:The highly CB2 selective cannabinoid receptor inverse agonist, 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic acid N-benzo[1,3]dioxol-5-ylmethyl)amide (JTE-907; 9b), served as the lead compound for investigating the structure-activity relationships of its analogues and in the search for more potent and ...

journal_title：Journal of medicinal chemistry

authors： Raitio KH,Savinainen JR,Vepsäläinen J,Laitinen JT,Poso A,Järvinen T,Nevalainen T

更新日期：2006-03-23 00:00:00

abstract：:A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured...

journal_title：Journal of medicinal chemistry

authors： Peng X,Knapp BI,Bidlack JM,Neumeyer JL

更新日期：2006-01-12 00:00:00

abstract：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

journal_title：Journal of medicinal chemistry

authors： Hulshoff A,Perrin JH

更新日期：1977-03-01 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：:N-Methyl-d-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain NMDA receptors in the activated "open channel" state would be u...

journal_title：Journal of medicinal chemistry

authors： Naumiec GR,Jenko KJ,Zoghbi SS,Innis RB,Cai L,Pike VW

更新日期：2015-12-24 00:00:00

abstract：:This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of...

journal_title：Journal of medicinal chemistry

authors： Ettari R,Micale N,Schirmeister T,Gelhaus C,Leippe M,Nizi E,Di Francesco ME,Grasso S,Zappalà M

更新日期：2009-04-09 00:00:00

abstract：:The synthesis of a series N-(4-piperidinyl)-1H-benzimidazol-2-amines and the preliminary evaluation of their in vitro and in vivo antihistaminic activity are described. Cyclodesulfurization of (2-aminophenyl)thioureas with mercury(II) oxide resulted in 2-aminobenzimidazole intermediates, which were monoalkylated on th...

journal_title：Journal of medicinal chemistry

authors： Janssens F,Torremans J,Janssen M,Stokbroekx RA,Luyckx M,Janssen PA

更新日期：1985-12-01 00:00:00

abstract：:Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, is a member of the Tec family of kinases. BTK plays an essential role in B cell receptor (BCR)-mediated signaling as well as Fcγ receptor signaling in monocytes and Fcε receptor signaling in mast cells and basophils, all of which have been implicated in th...

journal_title：Journal of medicinal chemistry

authors： Watterson SH,De Lucca GV,Shi Q,Langevine CM,Liu Q,Batt DG,Beaudoin Bertrand M,Gong H,Dai J,Yip S,Li P,Sun D,Wu DR,Wang C,Zhang Y,Traeger SC,Pattoli MA,Skala S,Cheng L,Obermeier MT,Vickery R,Discenza LN,D'Arien

更新日期：2016-10-13 00:00:00

abstract：:2-Hydroxy-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H- pyrrolizine bis(2-propylcarbamate) (11) was prepared in a multistep synthesis. The 2-hydroxy group was used to prepare ester prodrugs 14 and 15, and the antineoplastic activities of 11, 14, and 15a were compared to 1 (the 2-deoxy analogue of 11) i...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Chang CP,McPherson HL Jr

更新日期：1983-09-01 00:00:00

abstract：:Two new analogues derived from the platelet activating factor (PAF), containing glucosamine instead of the acetyl group, were synthesized, and their effect on the human keratinocyte cell line HaCaT was evaluated with respect to cytotoxicity, proliferation, adhesion, and migration. Starting with (R)-1,2-isopropylideneg...

journal_title：Journal of medicinal chemistry

authors： Bartolmäs T,Heyn T,Mickeleit M,Fischer A,Reutter W,Danker K

更新日期：2005-10-20 00:00:00

abstract：:MbtA (a salicyl AMP ligase) is a key target for the design of new antitubercular agents. On the basis of structure-activity relationship (SAR) data generated in our laboratory, a structure-based model is developed to predict the binding affinities of aryl acid-AMP bisubstrate inhibitors of MbtA. The approach described...

journal_title：Journal of medicinal chemistry

authors： Labello NP,Bennett EM,Ferguson DM,Aldrich CC

更新日期：2008-11-27 00:00:00

abstract：:Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic inter...

journal_title：Journal of medicinal chemistry

authors： Antoon JW,Liu J,Gestaut MM,Burow ME,Beckman BS,Foroozesh M

更新日期：2009-09-24 00:00:00

abstract：:A series of 1-amino- and 1-mercapto-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyrans was synthesized and subsequently evaluated in three rodent test systems for CNS activity. The structure-activity data generated indicate that, in general, a change of the 1-hydroxy group to an amine results in a retention of pharmacological ...

journal_title：Journal of medicinal chemistry

authors： Matsumoto K,Stark P,Meister RG

更新日期：1977-01-01 00:00:00