Fluoronaphthyridines as antibacterial agents. 6. Synthesis and structure-activity relationships of new chiral 7-(1-, 3-, 4-, and 6-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)naphthyridine analogues of 7-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-1-(1,1-

abstract：:The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or...

journal_title：Journal of medicinal chemistry

authors： Moloney GP,Robertson AD,Martin GR,MacLennan S,Mathews N,Dodsworth S,Sang PY,Knight C,Glen R

更新日期：1997-07-18 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 series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal ...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Gadsby B

更新日期：1978-09-01 00:00:00

abstract：:Matrix metalloproteinases (MMPs) are a family of over 20 zinc-dependent enzymes that hydrolyze connective tissue and are involved in a variety of diseases, which are associated with undesired tissue breakdown. This paper reports the synthesis, characterization, and biological evaluation of a novel class of MMP inhibit...

journal_title：Journal of medicinal chemistry

authors： Breuer E,Salomon CJ,Katz Y,Chen W,Lu S,Röschenthaler GV,Hadar R,Reich R

更新日期：2004-05-20 00:00:00

abstract：:A series of 2,3-diaminopropionanilides was synthesized by acylation of mono- and disubstituted aniline derivatives with 2,3-dibromopropionyl chloride and subsequent amination with the appropriate secondary amines. The target compounds were evaluated in mice for antiarrhythmic efficacy against chloroform-induced tachyc...

journal_title：Journal of medicinal chemistry

authors： Tenthorey PA,Adams HJ,Kronberg GH,Takman BH

更新日期：1981-09-01 00:00:00

abstract：:Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or ary...

journal_title：Journal of medicinal chemistry

authors： von Geldern TW,Kester JA,Bal R,Wu-Wong JR,Chiou W,Dixon DB,Opgenorth TJ

更新日期：1996-02-16 00:00:00

abstract：:By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7-(dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and...

journal_title：Journal of medicinal chemistry

authors： Kemnitzer W,Drewe J,Jiang S,Zhang H,Wang Y,Zhao J,Jia S,Herich J,Labreque D,Storer R,Meerovitch K,Bouffard D,Rej R,Denis R,Blais C,Lamothe S,Attardo G,Gourdeau H,Tseng B,Kasibhatla S,Cai SX

更新日期：2004-12-02 00:00:00

abstract：:The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by ...

journal_title：Journal of medicinal chemistry

authors： Secrist JA 3rd,Shortnacy AT,Montgomery JA

更新日期：1988-02-01 00:00:00

abstract：:A series of cyclopropane-based conformationally restricted analogues of histamine, the "folded" cis-analogues, i.e., (1S,2R)-2-(aminomethyl)-1-(1H-imidazol-4-yl)cyclopropane (11), (1S,2S)-2-(2-aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane (13), and their enantiomers ent-11 and ent-13, and the "extended" trans-analogues...

journal_title：Journal of medicinal chemistry

authors： Kazuta Y,Hirano K,Natsume K,Yamada S,Kimura R,Matsumoto S,Furuichi K,Matsuda A,Shuto S

更新日期：2003-05-08 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：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...

journal_title：Journal of medicinal chemistry

authors： Teng P,Huo D,Nimmagadda A,Wu J,She F,Su M,Lin X,Yan J,Cao A,Xi C,Hu Y,Cai J

更新日期：2016-09-08 00:00:00

abstract：:Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the...

journal_title：Journal of medicinal chemistry

authors： Razdan RK,Terris BZ,Pars HG,Plotnikoff NP,Dodge PW,Dren AT,Kyncl J,Somani P

更新日期：1976-04-01 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

abstract：:CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of C...

journal_title：Journal of medicinal chemistry

authors： Smith EW,Liu Y,Getschman AE,Peterson FC,Ziarek JJ,Li R,Volkman BF,Chen Y

更新日期：2014-11-26 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：:In this study we describe an extension of our previous studies on cis-benzylidenemalononitrile tyrphostins. We have introduced S-aryl substituents in the 5 position (meta vis-a-vis the malononitrile moiety). We find that these compounds are potent blockers of EGFR kinase and its homolog HER-2 kinase. Interestingly, we...

journal_title：Journal of medicinal chemistry

authors： Gazit A,Osherov N,Posner I,Bar-Sinai A,Gilon C,Levitzki A

更新日期：1993-11-12 00:00:00

abstract：:A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity re...

journal_title：Journal of medicinal chemistry

authors： Combs DW,Reese K,Cornelius LA,Gunnet JW,Cryan EV,Granger KS,Jordan JJ,Demarest KT

更新日期：1995-12-08 00:00:00

abstract：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...

journal_title：Journal of medicinal chemistry

authors： Monte AP,Marona-Lewicka D,Cozzi NV,Nichols DE

更新日期：1993-11-12 00:00:00

abstract：:A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...

journal_title：Journal of medicinal chemistry

authors： Mallo-Abreu A,Prieto-Díaz R,Jespers W,Azuaje J,Majellaro M,Velando C,García-Mera X,Caamaño O,Brea J,Loza MI,Gutiérrez-de-Terán H,Sotelo E

更新日期：2020-07-23 00:00:00

abstract：:Phenyl-substituted analogues of 2-[(phenylmethyl)sulfonyl]pyridine 1-oxide preemergent herbicides were examined in order to determine quantitative relationships between structure and activity against the following three weed species: switch grass (Panicum virgatum L.), barnyard grass (Echinochloa crusgalli L. Beauv.),...

journal_title：Journal of medicinal chemistry

authors： Doweyko AM,Bell AR,Minatelli JA,Relyea DI

更新日期：1983-04-01 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：:Selective inhibitors of protein tyrosine phosphatases (PTPs) and dual-specificity phosphatases (DSPs) are expected to be useful tools for clarifying the biological functions of the PTPs themselves and also to be candidates for novel therapeutics. We planned a library approach for the identification of PTP/DSP inhibito...

journal_title：Journal of medicinal chemistry

authors： Sodeoka M,Sampe R,Kojima S,Baba Y,Usui T,Ueda K,Osada H

更新日期：2001-09-27 00:00:00

abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Fry DW,Kraker AJ,Denny WA

更新日期：1994-03-04 00:00:00

abstract：:3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antag...

journal_title：Journal of medicinal chemistry

authors： Carling RW,Leeson PD,Moore KW,Smith JD,Moyes CR,Mawer IM,Thomas S,Chan T,Baker R,Foster AC

更新日期：1993-10-29 00:00:00

abstract：:To search for new antiestrogens more effective in treating breast cancers, we explored alternatives to the acrylic acid side chain used in many antiestrogens. To facilitate our search, we used a simple adamantyl ligand core that by avoiding stereochemical issues enabled rapid synthesis of acrylate ketone, ester, and a...

journal_title：Journal of medicinal chemistry

authors： Min J,Guillen VS,Sharma A,Zhao Y,Ziegler Y,Gong P,Mayne CG,Srinivasan S,Kim SH,Carlson KE,Nettles KW,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2017-07-27 00:00:00

abstract：:[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low p...

journal_title：Journal of medicinal chemistry

authors： Kohl B,Sturm E,Senn-Bilfinger J,Simon WA,Krüger U,Schaefer H,Rainer G,Figala V,Klemm K

更新日期：1992-03-20 00:00:00

abstract：:Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Bagal SK,Bickerton S,Bodnarchuk MS,Breed J,Carbajo RJ,Cassar DJ,Chakraborty A,Cosulich S,Cumming I,Davies M,Eatherton A,Evans L,Feron L,Fillery S,Gleave ES,Goldberg FW,Harlfinger S,Hanson L,Howard M,Howe

更新日期：2020-05-14 00:00:00

abstract：:Protease activated receptors (PARs) or thrombin receptors constitute a class of G-protein-coupled receptors (GPCRs) implicated in the activation of many physiological mechanisms. Thus, thrombin activates many cell types such as vascular smooth muscle cells, leukocytes, endothelial cells, and platelets via activation o...

journal_title：Journal of medicinal chemistry

authors： Perez M,Lamothe M,Maraval C,Mirabel E,Loubat C,Planty B,Horn C,Michaux J,Marrot S,Letienne R,Pignier C,Bocquet A,Nadal-Wollbold F,Cussac D,de Vries L,Le Grand B

更新日期：2009-10-08 00:00:00

abstract：:A variety of esters of methyldopa was synthesized with the objective of obtaining derivatives that would be more efficiently absorbed from the gastrointestinal tract than the free amino acid and would undergo conversion to methyldopa readily in the blood or target tissues. Two of the esters, alpha-pivaloyloxyethyl (4u...

journal_title：Journal of medicinal chemistry

authors： Saari WS,Freedman MB,Hartman RD,King SW,Raab AW,Randall WC,Engelhardt EL,Hirschmann R,Rosegay A,Ludden CT,Scriabine A

更新日期：1978-08-01 00:00:00

abstract：:FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophospho...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Uecker A,Sellmer A,Cénac C,Höcher H,Pongratz H,Eichhorn E,Hufsky H,Trümpler A,Sicker M,Heidel F,Fischer T,Stocking C,Elz S,Böhmer FD,Dove S

更新日期：2006-06-01 00:00:00