Identification of peptide substrate and small molecule inhibitors of testis-specific serine/threonine kinase1 (TSSK1) by the developed assays.

abstract：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

journal_title：Journal of medicinal chemistry

authors： Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

更新日期：1979-06-01 00:00:00

abstract：:The synthesis and biological evaluation of a series of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), the only benzodiazepine that acts simultaneously as a kappa-opioid agonist and a cholecystokinin-A (CCK-A) antagonist, are reported. The radioligand binding models used in these stu...

journal_title：Journal of medicinal chemistry

authors： Cappelli A,Anzini M,Vomero S,Menziani MC,De Benedetti PG,Sbacchi M,Clarke GD,Mennuni L

更新日期：1996-02-16 00:00:00

abstract：:ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal...

journal_title：Journal of medicinal chemistry

authors： de Leeuw M,González A,Lanir A,Roiz L,Smirnoff P,Schwartz B,Shoseyov O,Almog O

更新日期：2012-02-09 00:00:00

abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...

journal_title：Journal of medicinal chemistry

authors： Corea G,Fattorusso E,Lanzotti V,Motti R,Simon PN,Dumontet C,Di Pietro A

更新日期：2004-02-12 00:00:00

abstract：:In this study we present the synthesis and some pharmacological properties of nine new analogues of arginine vasopressin modified in the N-terminal part of the molecule with 2-aminoindane-2-carboxylic acid (Aic). The peptides were tested for their in vitro uterotonic and in vivo pressor and antidiuretic activities. On...

journal_title：Journal of medicinal chemistry

authors： Kowalczyk W,Sobolewski D,Prahl A,Derdowska I,Borovicková L,Slaninová J,Lammek B

更新日期：2007-06-14 00:00:00

abstract：:K-Ras is one of the most frequently mutated signal transducing human oncogenes. Ras signaling activity requires correct cellular localization of the GTPase. The spatial organization of K-Ras is controlled by the prenyl binding protein PDEδ, which enhances Ras diffusion in the cytosol. Inhibition of the Ras-PDEδ intera...

journal_title：Journal of medicinal chemistry

authors： Zimmermann G,Schultz-Fademrecht C,Küchler P,Murarka S,Ismail S,Triola G,Nussbaumer P,Wittinghofer A,Waldmann H

更新日期：2014-06-26 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：:MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the c...

journal_title：Journal of medicinal chemistry

authors： Li W,Li J,Wu Y,Rancati F,Vallese S,Raveglia L,Wu J,Hotchandani R,Fuller N,Cunningham K,Morgan P,Fish S,Krykbaev R,Xu X,Tam S,Goldman SJ,Abraham W,Williams C,Sypek J,Mansour TS

更新日期：2009-09-10 00:00:00

abstract：:We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucag...

journal_title：Journal of medicinal chemistry

authors： Sturm NS,Lin Y,Burley SK,Krstenansky JL,Ahn JM,Azizeh BY,Trivedi D,Hruby VJ

更新日期：1998-07-16 00:00:00

abstract：:The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the ...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Quincy DA,Lane B,Mollison KW,Or YS,Luly JR,Carter GW

更新日期：1992-01-24 00:00:00

abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...

journal_title：Journal of medicinal chemistry

authors： Yang SP,Zhang XW,Ai J,Gan LS,Xu JB,Wang Y,Su ZS,Wang L,Ding J,Geng MY,Yue JM

更新日期：2012-09-27 00:00:00

abstract：:A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3 alpha, 4 beta, 5 alpha)]-2-amino-1, 9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereo...

journal_title：Journal of medicinal chemistry

authors： Tino JA,Clark JM,Field AK,Jacobs GA,Lis KA,Michalik TL,McGeever-Rubin B,Slusarchyk WA,Spergel SH,Sundeen JE

更新日期：1993-04-30 00:00:00

abstract：:Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...

journal_title：Journal of medicinal chemistry

authors： Pouliot M,Jeanmart S

更新日期：2016-01-28 00:00:00

abstract：:The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and...

journal_title：Journal of medicinal chemistry

authors： Pommery N,Taverne T,Telliez A,Goossens L,Charlier C,Pommery J,Goossens JF,Houssin R,Durant F,Hénichart JP

更新日期：2004-12-02 00:00:00

abstract：:The interaction between leukocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory and immune diseases. Recently, a novel series of p-arylthio cinnamides has been described as potent antagonists of the LFA-1/ICAM-1 interaction. These compounds wer...

journal_title：Journal of medicinal chemistry

authors： Liu G,Huth JR,Olejniczak ET,Mendoza R,DeVries P,Leitza S,Reilly EB,Okasinski GF,Fesik SW,von Geldern TW

更新日期：2001-04-12 00:00:00

abstract：:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compo...

journal_title：Journal of medicinal chemistry

authors： Graham SL,Hoffman JM,Gautheron P,Michelson SR,Scholz TH,Schwam H,Shepard KL,Smith AM,Smith RL,Sondey JM

更新日期：1990-02-01 00:00:00

abstract：:Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated clinical efficacy in the treatment of acute migraine. Herein, we describe the design, synthesis, and preclinical characterization of a highly potent, oral CGRP receptor antagonist BMS-927711 (8). Compound 8 has good oral bioavailability in r...

journal_title：Journal of medicinal chemistry

authors： Luo G,Chen L,Conway CM,Denton R,Keavy D,Signor L,Kostich W,Lentz KA,Santone KS,Schartman R,Browning M,Tong G,Houston JG,Dubowchik GM,Macor JE

更新日期：2012-12-13 00:00:00

abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

journal_title：Journal of medicinal chemistry

authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

更新日期：2016-10-13 00:00:00

abstract：:3-O-tert-Butylmorphine (5) was prepared from 6-O-acetylmorphine (3) via alkylation with N,N-dimethylformamide di-tert-butyl acetal, followed by hydrolytic removal of the 3-(dimethylamino)-2-propenoate group. The same process was used to prepare the tert-butyl ether of levorphanol (6), (-)-3-tert-butoxy-N-methylmorphin...

journal_title：Journal of medicinal chemistry

authors： Mohacsi E,Leimgruber W,Baruth H

更新日期：1982-10-01 00:00:00

abstract：:In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding assays in CHO c...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Antonello A,Cavalli A,Bolognesi ML,Minarini A,Marucci G,Poggesi E,Leonardi A,Melchiorre C

更新日期：2003-11-06 00:00:00

abstract：:A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (pht...

journal_title：Journal of medicinal chemistry

authors： Hu M,Brasseur N,Yildiz SZ,van Lier JE,Leznoff CC

更新日期：1998-05-21 00:00:00

abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...

journal_title：Journal of medicinal chemistry

authors： Kees KL,Caggiano TJ,Steiner KE,Fitzgerald JJ Jr,Kates MJ,Christos TE,Kulishoff JM Jr,Moore RD,McCaleb ML

更新日期：1995-02-17 00:00:00

abstract：:(-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's d...

journal_title：Journal of medicinal chemistry

authors： Naidoo J,De Jesus-Cortes H,Huntington P,Estill S,Morlock LK,Starwalt R,Mangano TJ,Williams NS,Pieper AA,Ready JM

更新日期：2014-05-08 00:00:00

abstract：:An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to ...

journal_title：Journal of medicinal chemistry

authors： Cushman M,Nagarathnam D,Gopal D,Chakraborti AK,Lin CM,Hamel E

更新日期：1991-08-01 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:Ruthenium polypyridyl complexes show great promise as new photodynamic therapy (PDT) agents. However, a lack of detailed understanding of their mode of action in cells poses a challenge to their development. We have designed a new Ru(II) PDT candidate that efficiently enters cells by incorporation of the lipophilic ar...

journal_title：Journal of medicinal chemistry

authors： Cloonan SM,Elmes RB,Erby M,Bright SA,Poynton FE,Nolan DE,Quinn SJ,Gunnlaugsson T,Williams DC

更新日期：2015-06-11 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:In our search for potent and receptor-selective agonists and antagonists, we report here the results of D-amino acid substitution at each position of the short peptide gamma-melanocyte-stimulating hormone (gamma-MSH). The native gamma-MSH shows weak binding at all three receptors (i.e., the human MC3, MC4, and MC5) an...

journal_title：Journal of medicinal chemistry

authors： Grieco P,Balse PM,Weinberg D,MacNeil T,Hruby VJ

更新日期：2000-12-28 00:00:00

abstract：:New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affin...

journal_title：Journal of medicinal chemistry

authors： Crosignani S,Prêtre A,Jorand-Lebrun C,Fraboulet G,Seenisamy J,Augustine JK,Missotten M,Humbert Y,Cleva C,Abla N,Daff H,Schott O,Schneider M,Burgat-Charvillon F,Rivron D,Hamernig I,Arrighi JF,Gaudet M,Zimmerli SC,Jui

更新日期：2011-10-27 00:00:00

abstract：:Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic disea...

journal_title：Journal of medicinal chemistry

authors： Salado IG,Singh AK,Moreno-Cinos C,Sakaine G,Siderius M,Van der Veken P,Matheeussen A,van der Meer T,Sadek P,Gul S,Maes L,Sterk GJ,Leurs R,Brown D,Augustyns K

更新日期：2020-04-09 00:00:00