Synthesis and physicochemical properties of sulfamate derivatives as topical antiglaucoma agents.

abstract：:A new series of calcium channel agonists structurally related to Bay K8644, containing NO donor furoxans and the related furazans unable to release NO, is described. The racemic mixtures were studied for their action on L-type Ca(2+) channels expressed in cultured rat insulinoma RINm5F cells. All the products proved t...

journal_title：Journal of medicinal chemistry

authors： Visentin S,Rolando B,Di Stilo A,Fruttero R,Novara M,Carbone E,Roussel C,Vanthuyne N,Gasco A

更新日期：2004-05-06 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 series of methanoprolinenitrile-containing dipeptide mimetics were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV (DPP-IV). The catalytic action of DPP-IV is the principle means of degradation of glucagon-like peptide-1, a key mediator of glucose-sti...

journal_title：Journal of medicinal chemistry

authors： Magnin DR,Robl JA,Sulsky RB,Augeri DJ,Huang Y,Simpkins LM,Taunk PC,Betebenner DA,Robertson JG,Abboa-Offei BE,Wang A,Cap M,Xin L,Tao L,Sitkoff DF,Malley MF,Gougoutas JZ,Khanna A,Huang Q,Han SP,Parker RA,Hamann LG

更新日期：2004-05-06 00:00:00

abstract：:The poor solubility of the thymidylate synthase (TS) inhibiting antifolate 10-propargyl-5,8-dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3,4-dihydro-4-oxopyrimidine moiety of the drug which stabilizes the solid s...

journal_title：Journal of medicinal chemistry

authors： Jones TR,Thornton TJ,Flinn A,Jackman AL,Newell DR,Calvert AH

更新日期：1989-04-01 00:00:00

abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...

journal_title：Journal of medicinal chemistry

authors： Mbatia HW,Ramalingam S,Ramamurthy VP,Martin MS,Kwegyir-Afful AK,Njar VC

更新日期：2015-02-26 00:00:00

abstract：:Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0...

journal_title：Journal of medicinal chemistry

authors： Law SJ,Morgan JM,Masten LW,Borne RF,Arana GW,Kula NS,Baldessarini RJ

更新日期：1982-03-01 00:00:00

abstract：:A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyl...

journal_title：Journal of medicinal chemistry

authors： Houston DM,Matuszewska B,Borchardt RT

更新日期：1985-04-01 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 00:00:00

abstract：:HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to comb...

journal_title：Journal of medicinal chemistry

authors： Velázquez F,Sannigrahi M,Bennett F,Lovey RG,Arasappan A,Bogen S,Nair L,Venkatraman S,Blackman M,Hendrata S,Huang Y,Huelgas R,Pinto P,Cheng KC,Tong X,McPhail AT,Njoroge FG

更新日期：2010-04-22 00:00:00

abstract：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...

journal_title：Journal of medicinal chemistry

authors： Borsari C,Rageot D,Dall'Asen A,Bohnacker T,Melone A,Sele AM,Jackson E,Langlois JB,Beaufils F,Hebeisen P,Fabbro D,Hillmann P,Wymann MP

更新日期：2019-09-26 00:00:00

abstract：:Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a consequence of the low-lying σ* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, π-systems. Intramolecular interactions are by far the most ...

journal_title：Journal of medicinal chemistry

authors： Beno BR,Yeung KS,Bartberger MD,Pennington LD,Meanwell NA

更新日期：2015-06-11 00:00:00

abstract：:The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it ...

journal_title：Journal of medicinal chemistry

authors： Russell MG,Carling RW,Street LJ,Hallett DJ,Goodacre S,Mezzogori E,Reader M,Cook SM,Bromidge FA,Newman R,Smith AJ,Wafford KA,Marshall GR,Reynolds DS,Dias R,Ferris P,Stanley J,Lincoln R,Tye SJ,Sheppard WF,Sohal B,

更新日期：2006-02-23 00:00:00

abstract：:5-Aroyl-6-substituted-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carbo xylic acids were synthesized and assayed for analgesic and antiinflammatory activity. Several of these compounds, notably the 5-(4-fluoro- and 4-chlorobenzoyl)-6-methyl derivatives 25 and 26 and the 5-(4-methyl-, 4-fluoro-, 4-chloro-, and 4-methoxybenz...

journal_title：Journal of medicinal chemistry

authors： Muchowski JM,Cooper GF,Halpern O,Koehler R,Kluge AF,Simon RL,Unger SH,Van Horn AR,Wren DL,Ackrell J

更新日期：1987-05-01 00:00:00

abstract：:2-Phenylcyclopropylmethylamine (PCPMA) analogues have been reported as selective serotonin 2C agonists. On the basis of the same scaffold, we designed and synthesized a series of bitopic derivatives as dopamine D3R ligands. A number of these new compounds show a high binding affinity for D3R with excellent selectivity...

journal_title：Journal of medicinal chemistry

authors： Tan L,Zhou Q,Yan W,Sun J,Kozikowski AP,Zhao S,Huang XP,Cheng J

更新日期：2020-05-14 00:00:00

abstract：:Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock sei...

journal_title：Journal of medicinal chemistry

authors： Cortes S,Liao ZK,Watson D,Kohn H

更新日期：1985-05-01 00:00:00

abstract：:Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p...

journal_title：Journal of medicinal chemistry

authors： Fási L,Di Meo F,Kuo CY,Stojkovic Buric S,Martins A,Kúsz N,Béni Z,Dékány M,Balogh GT,Pesic M,Wang HC,Trouillas P,Hunyadi A

更新日期：2019-02-14 00:00:00

abstract：:The receptor CRM1 is responsible for the nuclear export of many tumor-suppressor proteins and viral ribonucleoproteins. This renders CRM1 an interesting target for therapeutic intervention in diverse cancer types and viral diseases. Structural studies of Saccharomyces cerevisiae CRM1 ( Sc ...

journal_title：Journal of medicinal chemistry

authors： Shaikhqasem A,Dickmanns A,Neumann P,Ficner R

更新日期：2020-07-23 00:00:00

abstract：:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poi...

journal_title：Journal of medicinal chemistry

authors： Margel S

更新日期：1981-10-01 00:00:00

abstract：:Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In t...

journal_title：Journal of medicinal chemistry

authors： Hajduk PJ

更新日期：2006-11-30 00:00:00

abstract：:The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid-peptide conjugates (CAPs), demonstrating that valine-glycine dipeptide-derived CAP 3 is the most ...

journal_title：Journal of medicinal chemistry

authors： Yadav K,Kumar S,Mishra D,Asad M,Mitra M,Yavvari PS,Gupta S,Vedantham M,Ranga P,Komalla V,Pal S,Sharma P,Kapil A,Singh A,Singh N,Srivastava A,Thukral L,Bajaj A

更新日期：2019-02-28 00:00:00

abstract：:2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyan...

journal_title：Journal of medicinal chemistry

authors： Matsuda A,Dan A,Minakawa N,Tregear SJ,Okazaki S,Sugimoto Y,Sasaki T

更新日期：1993-12-24 00:00:00

abstract：:Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator...

journal_title：Journal of medicinal chemistry

authors： García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos A

更新日期：2005-06-16 00:00:00

abstract：:A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at...

journal_title：Journal of medicinal chemistry

authors： Shaw DE,Baig F,Bruce I,Chamoin S,Collingwood SP,Cross S,Dayal S,Drückes P,Furet P,Furminger V,Haggart D,Hussey M,Konstantinova I,Loren JC,Molteni V,Roberts S,Reilly J,Saunders AM,Stringer R,Sviridenko L,Thomas M,

更新日期：2016-09-08 00:00:00

abstract：:7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28). In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha 2-adrenoceptor (PNMT Ki = 0....

journal_title：Journal of medicinal chemistry

authors： Grunewald GL,Dahanukar VH,Caldwell TM,Criscione KR

更新日期：1997-12-05 00:00:00

abstract：:Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-...

journal_title：Journal of medicinal chemistry

authors： Hoekstra WJ,Maryanoff BE,Damiano BP,Andrade-Gordon P,Cohen JH,Costanzo MJ,Haertlein BJ,Hecker LR,Hulshizer BL,Kauffman JA,Keane P,McComsey DF,Mitchell JA,Scott L,Shah RD,Yabut SC

更新日期：1999-12-16 00:00:00

abstract：:A representative series of 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes was synthesized and evaluated in vitro, as well as in vivo, as potential analgetic agents. In general, moderate to good activity (19 twice as active as morphine) was observed in the phenylquinone writhing assay (PQW), while only marginal activit...

journal_title：Journal of medicinal chemistry

authors： Ong HH,Anderson VB,Wilker JC,Spaulding TC,Meyerson LR

更新日期：1980-07-01 00:00:00

abstract：:The first synthesis of the tamoxifen metabolite norendoxifen is reported. This included syntheses of (E)-norendoxifen, (Z)-norendoxifen, and (E,Z)-norendoxifen isomers. (Z)-Norendoxifen displayed affinity for aromatase (Ki 442 nM), estrogen receptor-α (EC50 17 nM), and estrogen receptor-β (EC50 27.5 nM), while the cor...

journal_title：Journal of medicinal chemistry

authors： Lv W,Liu J,Lu D,Flockhart DA,Cushman M

更新日期：2013-06-13 00:00:00

abstract：:A rapid, efficient procedure useful for the radiosynthesis of [Me-3H]-MPDP+ ([methyl-3H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me-3H]-MPTP to its corresponding radiolabeled N-oxide. ...

journal_title：Journal of medicinal chemistry

authors： Cashman JR

更新日期：1988-06-01 00:00:00

abstract：:The paullones represent a novel class of small molecule cyclin-dependent kinase (CDK) inhibitors. To investigate structure-activity relationships and to develop paullones with antitumor activity, derivatives of the lead structure kenpaullone (9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, 4a) were synthesiz...

journal_title：Journal of medicinal chemistry

authors： Schultz C,Link A,Leost M,Zaharevitz DW,Gussio R,Sausville EA,Meijer L,Kunick C

更新日期：1999-07-29 00:00:00

abstract：:Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D...

journal_title：Journal of medicinal chemistry

authors： Fontenla JA,Osuna J,Rosa E,Castro ME,G-Ferreiro T,Loza-García I,Calleja JM,Sanz F,Rodríguez J,Raviña E

更新日期：1994-08-05 00:00:00